Colorimetric artificial nose having an array of dyes and method for artificial olfaction

ABSTRACT

The present invention involves an artificial nose having an array comprising at least a first dye and a second dye in combination and having a distinct spectral response to an analyte. In one embodiment, the first and second dyes are from the group comprising chemoresponsive dyes, and the second dye is distinct from the first dye. In one embodiment, the first dye is selected from the group consisting of porphyrin, chlorin, chlorophyll, phthalocyanine, and salen, or their metal complexes. In another embodiment, the second dye is selected from the group of dyes consisting of acid-base indicator dyes and solvatochromic dyes. The present invention is particularly useful in detecting metal ligating vapors. Further, the array of the present invention can be connected to a visual display device.

CONTINUING APPLICATION DATA

[0001] This application is a Continuation-in-Part of U.S. applicationSer. No. 09/705,329, filed on Nov. 3, 2000, which is aContinuation-in-Part of U.S. application Ser. No. 09/532,125, filed onMar. 21, 2000, now U.S. Pat. No. 6,368,558.

[0002] This invention was made with Government support under ContractNos. HL25934 awarded by the National Institutes of Health & Contract No.DAAG55-97-1-2211 awarded by the Department of the Army. The Governmenthas certain rights in the invention.

FIELD OF THE INVENTION

[0003] The present invention relates to methods and apparatus forartificial olfaction, e.g., artificial noses, for the detection ofodorants by a visual display.

BACKGROUND OF THE INVENTION

[0004] There is a great need for olfactory or vapor-selective detectors(i.e., “artificial noses”) in a wide variety of applications. Forexample, there is a need for artificial noses that can detect low levelsof odorants and/or where odorants may be harmful to humans, animals orplants. Artificial noses that can detect many different chemicals aredesirable for personal dosimeters in order to detect the type and amountof odorants exposed to a human, the presence of chemical poisons ortoxins, the spoilage in foods, the presence of flavorings, or thepresence of vapor emitting items, such as plant materials, fruits andvegetables, e.g., at customs portals.

[0005] Conventional artificial noses have severe limitations anddisadvantages and are not considered generally useful for such purposes.Limitations and disadvantages of conventional artificial noses includetheir need for extensive signal transduction hardware, and theirinability to selectively target metal-coordinating vapors and toxins. Inaddition, artificial noses which incorporate mass sensitive signaltransduction or polar polymers as sensor elements are susceptible tointerference by water vapor. This limitation is significant in that itcan cause variable response of the detector with changes ambienthumidity. See F. L. Dickert, O. Hayden, Zenkel, M. E. Anal. Chem. 71,1338 (1999).

[0006] Initial work in the field of artificial noses was conducted byWilkens and Hatman in 1964, though the bulk of research done in thisarea has been carried out since the early 1980's. See, e.g., W. F.Wilkens, A. D. Hatman. Ann. NY Acad. Sci., 116, 608 (1964); K. Pursaud,G. H. Dodd. Nature, 299, 352-355 (1982); and J. W. Gardner, P. N.Bartlett. Sensors and Actuators B, 18-19, 211-220 (1994).

[0007] Vapor-selective detectors or “artificial noses” are typicallybased upon the production of an interpretable signal or display uponexposure to a vapor emitting substance or odorant (hereinafter sometimesreferred to as an “analyte”). More specifically, typical artificialnoses are based upon selective chemical binding or an interface betweena detecting compound of the artificial nose and an analyte or odorant,and then transforming that chemical binding into a signal or display,i.e., signal transduction.

[0008] Polymer arrays having a single dye have been used for artificialnoses. That is, a series of chemically-diverse polymers or polymerblends are chosen so that their composite response distinguishes a givenodorant or analyte from others. Examples of polymer array vapordetectors, including conductive polymer and conductive polymer/carbonblack composites, are discussed in: M. S. Freund, N. S. Lewis, Proc.Natl. Acad. Sci. USA 92, 2652-2656 (1995); B. J. Doleman, R. D. Sanner,E. J. Severin, R. H. Grubbs, N. S. Lewis, Anal. Chem. 70, 2560-2564(1998); T. A. Dickinson, J. White, J. S. Kauer, D. R. Walt, Nature 382,697-700 (1996)(polymer array with optical detection); A. E. Hoyt, A. J.Ricco, H. C. Yang, R. M. Crooks, J. Am. Chem. Soc. 117, 8672 (1995); andJ. W. Grate, M. H. Abraham, Sensors and Actuators B 3, 85-111 (1991).

[0009] Other interface materials include functionalized self-assembledmonolayers (SAM), metal oxides, and dendrimers. Signal transduction iscommonly achieved with mass sensitive piezoelectric substrates, surfaceacoustic wave (SAW) transducers, or conductive materials. Opticaltransducers (based on absorbance or luminescence) have also beenexamined. Examples of metal oxide, SAM, and dendrimer-based detectorsare discussed in J. W. Gardner, H. V. Shurmer, P. Corcoran, SensorsandActuators B 4, 117-121 (1991); J. W. Gardner, H. V. Shurmer, T. T.Tan, Sensors and Actuators B 6, 71-75 (1992); and R. M. Crooks, A. J.Ricco, Acc. Chem. Res. 31, 219-227 (1998). These devices also use asingle dye.

[0010] Techniques have also been developed using a metalloporphyrin foroptical detection of a specific, single gas such as oxygen or ammonia,and for vapor detection by chemically interactive layers on quartzcrystal microbalances. See A. E. Baron, J. D. S. Danielson, M.Gouterman, J. R. Wan, J. B. Callis, Rev. Sci. Instrum. 64, 3394-3402(1993); J. Kavandi, et al., Rev. Sci. Instrum. 61, 3340-3347 (1990); W.Lee, et al., J. Mater. Chem. 3, 1031-1035 (1993); A. A. Vaughan, M. G.Baron, R. Narayanaswamy, Anal Comm. 33, 393-396 (1996); J. A. J.Brunink, et al., Anal. Chim. Acta 325, 53-64 (1996); C. DiNatale, etal., Sensors and Actuators B 44, 521-526 (1997); and C. DiNatale, etal., Mat. Sci. Eng. C 5, 209-215 (1998). However, these techniqueseither require extensive signal transduction hardware, or, as notedabove, are limited to the detection of a specific, single gas. They arealso subject to water vapor interference problems, as discussedpreviously.

[0011] While typical systems to date have demonstrated some success inchemical vapor detection and differentiation, these systems have focusedon the detection of non-metal binding or non-metal ligating solventvapors, such as arenes, halocarbons and ketones. Detection ofmetal-ligating vapors (such as amines, thiols, and phosphines) has beenmuch less explored. Further, while some single porphyrin based sensorshave been used for detection of a single strong acid, there is a needfor sensor devices that will detect a wide variety of vapors.

[0012] To summarize, there are a number of limitations and drawbacks totypical artificial noses and single porphyrin based sensors. As notedabove typical artificial noses are not designed for metal binding andmetal ligating vapors, such as amines, thiols, and phosphines. Further,typical artificial noses require extensive signal transduction hardware,and are subject to interference from water vapor. As noted above, singleporphyrin based sensors have been used for detection of a single strongacid, but cannot detect a wide variety of vapors. Thus, there is a needfor new artificial noses and methods that overcome these and otherlimitations of prior artificial noses and single porphyrin based sensorsand methods.

SUMMARY OF THE INVENTION

[0013] The present invention comprises an array of dyes including atleast a first dye and a second dye which in combination provide aspectral response distinct to an analyte or odorant. The dyes of thepresent invention produce a response in the spectrum range of about 200nanometers to 2,000 nanometers, which includes the visible spectrum oflight. It has now been discovered that an array of two or more dyesresponds to a given ligating species with a unique color patternspectrally and in a time dependent manner. Thus, dyes in the array ofthe present invention are capable of changing color in a distinct mannerwhen exposed to any one analyte or odorant. The pattern of colorsmanifested by the multiple dyes is indicative of a specific or givenanalyte. In other words, the pattern of dye colors observed isindicative of a particular vapor or liquid species.

[0014] In a preferred embodiment, the dyes of the array are porphyrins.In another preferred embodiment, the porphyrin dyes aremetalloporphyrins. In a further preferred embodiment, the array willcomprise ten to fifteen distinct metalloporphyrins in combination.Metalloporphyrins are preferable dyes in the present invention becausethey can coordinate metal-ligating vapors through open axialcoordination sites, and they produce large spectral shifts upon bindingof or interaction with metal-ligating vapors. In addition, porphyrins,metalloporphyrins, and many dyes show significant color changes uponchanges in the polarity of their environment; this so-calledsolvatochromic effect will give net color changes even in the absence ofdirect bonding between the vapor molecules and the metal ions. Thus,metalloporphyrins produce intense and distinctive changes in colorationupon ligand binding with metal ligating vapors.

[0015] The present invention provides a means for the detection ordifferentiation and quantitative measurement of a wide range of ligandvapors, such as amines, alcohols, and thiols. Further, the color dataobtained using the arrays of the present innovation may be used to givea qualitative fingerprint of an analyte, or may be quantitativelyanalyzed to allow for automated pattern recognition and/or determinationof analyte concentration. Because porphyrins also exhibit wavelength andintensity changes in their absorption bands with varying solventpolarity, weakly ligating vapors (e.g., arenes, halocarbons, or ketones)are also differentiable.

[0016] Diversity within the metalloporphyrin array may be obtained byvariation of the parent porphyrin, the porphyrin metal center, or theperipheral porphyrin substituents. The parent porphyrin is also referredto as a free base (“FB”) porphyrin, which has two central nitrogen atomsprotonated (i.e., hydrogen cations bonded to two of the central pyrrolenitrogen atoms). A preferred parent porphyrin is depicted in FIG. 2A,with the substitution of a two hydrogen ion for the metal ion (depictedas “M”) in the center of the porphyrin. In FIG. 2A, TTP stands for5,10,15,20-tetraphenylporphyrinate(-2).

[0017] In accordance with the present invention, calorimetric differencemaps can be generated by subtracting unexposed and exposedmetalloporphyrin array images (obtained, for example, with a commonflatbed scanner or inexpensive video or charge coupled device (“CCD”)detector) with image analysis software. This eliminates the need forextensive and expensive signal transduction hardware associated withprevious techniques (e.g., piezoelectric or semiconductor sensors). Bysimply differencing images of the array before and after exposure toanalytes, the present invention provides unique color change signaturesfor the analytes, for both qualitative recognition and quantitativeanalysis.

[0018] Sensor plates which incorporate vapor sensitive combinations ofdyes comprise an embodiment of the present invention which iseconomical, disposable, and can be utilized to provide qualitativeand/or quantitative identification of an analyte. In accordance with thepresent invention, a catalog of arrays and the resultant visual patternfor each analyte can be coded and placed in a look-up table or book forfuture reference. Thus, the present invention includes a method ofdetecting an analyte comprising the steps of forming an array of atleast a first dye and a second dye, subjecting the array to an analyte,inspecting the first and second dyes for a spectral response, andcomparing the spectral response with a catalog of analyte spectralresponses to identify the analyte.

[0019] Because sensing is based upon either covalent interaction (i.e.,ligation) or non-covalent solvation interactions between the analyte andthe porphyrin array, a broad spectrum of chemical species isdifferentiable. While long response times (e.g., about 45 minutes) areobserved at low analyte concentrations of about 1 ppm with reverse phasesilica gel plates, use of impermeable solid supports (such as polymer-or glass-based micro-array plates) substantially increases the low-levelresponse to less than 5 minutes.

[0020] Thus, it is an object of the present invention to provide methodsand devices for artificial olfaction, vapor-selective detectors orartificial noses for a wide variety of applications. It is anotherobject of the present invention to provide methods of detection andartificial noses that can detect low levels of odorants and/or whereodorants may be harmful to living human, animal or plant cells. It isalso an object of the present invention to provide methods of olfactorydetection and artificial noses that can detect and quantify manydifferent chemicals for dosimeters that can detect chemical poisons ortoxins, that can detect spoilage in foods, that can detect flavoringsand additives, and that can detect plant materials, e.g., fruits andvegetables.

[0021] Another object of the present invention is to provide for thedetection of analytes using data analysis/pattern recognitiontechniques, including automated techniques.

[0022] Another object of the invention is to provide an artificial nosecomprising an array, the array comprising at least a first dye and asecond dye deposited directly onto a single support in a predeterminedpattern combination, the combination of the dyes in the array having adistinct and direct spectral absorbance or reflectance response to ananalyte wherein the first dye and the second are selected from the groupof dyes consisting of chemoresponsive dyes, and the second dye isdistinct from the first dye. In one embodiment, the first dye isselected from the group consisting of porphyrin, chlorin, chlorophyll,phtahlocyanine, and salen and their metal complexes. In anotherembodiment, the second dye is selected from the group consisting ofacid-base indicator dyes and solvatochromic dyes.

[0023] Another object of the invention is to provide a method ofdetecting an analyte comprising the steps of: (a) forming an array of atleast a first dye and a second dye deposited directly onto a singlesupport in a predetermined pattern combination, the combination of thedyes in the array having a distinct and direct spectral absorbance orreflectance response to an analyte wherein the first dye and the seconddye are selected from the group consisting of chemoresponsive dyes, andthe second dye is distinct from the first dye, (b) subjecting the arrayto an analyte, (c) inspecting the array for a distinct and directspectral absorbance or reflectance response, and (d) correlating thedistinct and direct spectral response to the presence of the analyte. Inone embodiment, the first dye is selected from the group consisting ofporphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and theirmetal complexes. In another embodiment, the second dye is selected fromthe group consisting of acid-base indicator dyes and solvatochromicdyes.

[0024] Another object of the invention is to provide an artificialtongue comprising an array, the array comprising at least a first dyeand a second dye deposited directly onto a single support in apredetermined pattern combination, the combination of the dyes in thearray having a distinct and direct spectral absorbance or reflectanceresponse to an analyte wherein the first dye and the second are selectedfrom the group of dyes consisting of chemoresponsive dyes, and thesecond dye is distinct from the first dye. In one embodiment, the firstdye is selected from the group consisting of porphyrin, chlorin,chlorophyll, phtahlocyanine, and salen and their metal complexes. Inanother embodiment, the second dye is selected from the group consistingof acid-base indicator dyes and solvatochromic dyes.

BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The file of this patent contains at least one drawing executed incolor. Copies of this patent with color drawing(s) will be provided bythe Patent and Trademark Office upon request and payment of thenecessary fee.

[0026]FIG. 1 illustrates an embodiment of the optical sensing plate ofthe present invention using a first elution in the y axis and a secondelution in the x axis of the plate. In this embodiment the first elutionR—OH/hexane and the second elution is R—SH/hexane.

[0027]FIG. 2A illustrates an embodiment of the invention usingmetalloporphyrins as the sensing dyes.

[0028]FIG. 2B illustrates an embodiment of the invention usingmetalloporphyrins as the sensing dyes.

[0029]FIG. 3A illustrates a vapor exposure apparatus for demonstrationof the present invention.

[0030]FIG. 3B illustrates a vapor exposure apparatus for demonstrationof the present invention.

[0031]FIG. 4 illustrates the color change profile in a metalloporphyrinarray of FIG. 2 when used in the vapor exposure apparatus of FIG. 3A todetect n-butylamine. Metalloporphyrins were immobilized on reverse phasesilica gel plates.

[0032]FIG. 5 illustrates a comparison of color changes at saturation fora wide range of analytes. Each analyte was delivered to the array as anitrogen stream saturated with the analyte vapor at 20° C. DMF standsfor dimethylformamide; THF stands for tetrahydrofuran.

[0033]FIG. 6 illustrates two component saturation responses of mixturesof 2-methylpyridine and trimethylphosphite. Vapor mixtures were obtainedby mixing two analyte-saturated N₂ streams at variable flow ratios.

[0034]FIG. 7 illustrates a comparison of Zn(TPP) spectral shifts uponexposure to ethanol and pyridine (py) in methylene chloride solution (A)and on the reverse phase support (B).

[0035]FIG. 8 illustrates another embodiment of the present invention,and more particularly, an small array comprising microwells built into awearable detector which also contains a portable light source and alight detector, such as a charge-coupled device (CCD) or photodiodearray.

[0036]FIG. 9 illustrates another embodiment of the present invention,and more particularly, a microwell porphyrin array wellplate constructedfrom polydimethylsiloxane (PDMS).

[0037]FIG. 10 illustrates another embodiment of the present invention,and more particularly, a microplate containing machined teflon posts,upon which the porphyrin array is immobilized in a polymer matrix(polystyrene/dibutylphthalate).

[0038]FIG. 11 illustrates another embodiment of the present invention,showing a microplate of the type shown in FIG. 10, consisting of aminimized array of four metalloporphyrins, showing the color profilechanges for n-octylamine, dodecanethiol, and tri-n-butylphosphine, eachat 1.8 ppm.

[0039]FIG. 12 illustrates the immunity of the present invention tointerference from water vapor.

[0040]FIG. 13 illustrates the synthesis of siloxyl-substitutedbis-pocket porphyrins in accordance with the present invention.

[0041]FIGS. 14a, 14 b, and 14 c illustrate differences in K_(eq) forvarious porphyrins.

[0042]FIG. 15 illustrates molecular models of Zn(Si₆PP) (left column)and Zn(Si₈PP) (right column).

[0043]FIG. 16 illustrates an array containing illustrative examples ofporphyrin, metalloporphyrin, acid-base indicator, and solvatochromaticdyes.

[0044]FIG. 17 illustrates the response of the array described in FIG. 16to acid vapors, specifically formic acid, acetic acid, iso-valeric acid,and 3-methyl-2-hexenoic acid.

[0045]FIG. 18 illustrates a preferred array containing illustrativeexamples of porphyrin, metalloporphyrin, acid-base indicator, andsolvatochromatic dyes.

[0046]FIG. 19 illustrates the response of the array described in FIG. 18to acetone.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0047] Production of the Sensor Plate of the Present Invention

[0048] A sensor plate 10 fabricated in accordance with the presentinvention is shown in FIG. 1. Sensor plate 10 comprises atwo-dimensionally spatially resolved array 12 of various sensingelements or dyes 14 capable of changing color upon interaction (e.g.,binding, pi-pi complexation, or polarity induced shifts in color). Asshown in FIG. 1, a library of such dyes 14 can be given spatialresolution by two-dimensional chromatography or by direct deposition,including, but not limited to, ink-jet printing, micropipette spotting,screen printing, or stamping. In FIG. 1, metalloporphyrin mixture 6 isplaced at origin 7. Next, the metalloporphyrin mixture 6 is elutedthrough a silica gel or reversed-phase silica gel 5 in sensor plate 10,and the metalloporphyrins are spatially resolved from each other andimmobilized in silica gel 5 as depicted by the oval and circular shapes4 as shown in FIG. 1. Sensor plate 10 can be made from any suitablematerial or materials, including but not limited to, chromatographyplates, paper, filter papers, porous membranes, or properly machinedpolymers, glasses, or metals.

[0049]FIG. 1 also illustrates an embodiment of the optical sensing plateof the present invention using a first elution 8 in the y axis and asecond elution 9 in the x axis of sensor plate 10. In this embodiment,the first elution 8 is R—OH/hexane and the second elution 9 isR—SH/hexane. The order of the first and second elutions can be reversed.The first and second elutions are used to spatially resolve themetalloporphyrin mixture 6 in silica gel 5. As shown in FIG. 1, theupper left hand quadrant 3 is characterized by metalloporphyrins thatare “hard” selective, i.e., having a metal center having a high chemicalhardness, i.e., a high charge density. As shown in FIG. 1, the lowerright hand quadrant 2 is characterized by metalloporphyrins that are“soft” selective, i.e., having a metal center having a low chemicalhardness, i.e., a low charge density. In accordance with the presentinvention, the array can be a spatially resolved collection of dyes, andmore particularly a spatially resolved combinatorial family of dyes.

[0050] In accordance with the present invention, aporphyrin—metalloporphyrin sensor plate was prepared and then used todetect various odorants. More specifically, solutions of variousmetalated tetraphenylporphyrins in either methylene chloride orchlorobenzene were spotted in 1 μL aliquots onto two carbon (“C2”, i.e,ethyl-capped) reverse phase silica thin layer chromatography plates(Product No. 4809-800, by Whatman, Inc., Clifton, N.J.) to yield thesensor array 16 seen in FIG. 2B. As shown in FIG. 2B and summarized inTable 1 below, the dyes have the following colors (the exact colorsdepend, among other things, upon scanner settings). TABLE 1 (SummarizingColors of Dyes in FIG. 2B) Sn⁴⁺ — Green Co³⁺ — Red Cr³⁺ — Deep GreenMn³⁺ — Green Fe³⁺ — Dark Red Co²⁺ — Red Cu²⁺ — Red Ru²⁺ — Light YellowZn²⁺ — Greenish Red Ag²⁺ — Red 2H⁺ (Free Base “FB”) — Red

[0051] A metalloporphyrin 15, sometimes referred to as M(TPP), of thepresent invention is depicted in FIG. 2A. FIG. 2A also depicts variousmetals of the metalloporphyrins 15 of the present invention, andcorresponding metal ion charge to radius ratio (i.e., Z/r Ratio) inreciprocal angstroms. The Z/r Ratio should preferably span a wide rangein order to target a wide range of metal ligating analytes. Thesemetalloporphyrins have excellent chemical stability on the solid supportand most have well-studied solution ligation chemistry. Reverse phasesilica was chosen as a non-interacting dispersion medium for themetalloporphyrin array 16 depicted in FIG. 2B, as well as a suitablesurface for diffuse reflectance spectral measurements. More importantly,the reverse phase silica presents a hydrophobic interface, whichvirtually eliminates interference from ambient water vapor. Afterspotting, sensor plates 18 like the one depicted in FIG. 2B were driedunder vacuum at 50° C. for 1 hour prior to use. Thus, immobilization ofthe metalloporphyrins on a reverse phase silica support is obtained.While ten (10) different metalloporphyrins are shown in FIG. 2A, thoseof skill in the art will recognize that many other metalloporphyrins areuseful in accordance with the present invention. Those of skill in theart will further recognize that in accordance with the broad teachingsof the present invention, any dyes capable of changing color uponinteracting with an analyte, both containing and not containing metalions, are useful in the array of the present invention.

[0052] Colorimetric Analysis Using the Sensor Plate

[0053] For the detection and analysis of odorants in accordance with thepresent invention, one needs to monitor the absorbance of the sensorplate at one or more wavelengths in a spatially resolved fashion. Thiscan be accomplished with an imaging spectrophotometer, a simple flatbedscanner (e.g. a Hewlett Packard Scanjet 3c), or an inexpensive video orCCD camera.

[0054]FIG. 3A illustrates a vapor exposure apparatus 19 of the presentinvention. FIG. 3B illustrates top and side views of bottom piece 21 anda top view of top piece 21′ of a vapor exposure flow cell 20 of thepresent invention. In an embodiment of the present invention forpurposes of demonstration, each sensor plate 18 was placed inside of astainless steel flow cell 20 equipped with a quartz window 22 as shownin FIGS. 3A and 3B. Scanning of the sensor plate 18 was done on acommercially available flatbed scanner 24 (Hewlett Packard Scanjet 3c)at 200 dpi resolution, in full color mode. Following an initial scan, acontrol run with a first pure nitrogen flow stream 26 was performed. Thearray 16 of plate 18 was then exposed to a second nitrogen flow stream28 saturated with a liquid analyte 30 of interest. As shown in FIG. 3A,the nitrogen flow stream 28 saturated with liquid analyte 30 results ina saturated vapor 32. Saturated vapor 32, containing the analyte 30 ofinterest were generated by flowing nitrogen flow stream 28 at 0.47L/min. through the neat liquid analyte 30 in a water-jacketed, glassfritted bubbler 34. Vapor pressures were controlled by regulating thebubbler 34 temperature. As shown in FIG. 3B, vapor channels 23 permitvapor flow to sensor plate 18.

EXAMPLE 1

[0055] Scanning at different time intervals and subtracting the red,green and blue (“RGB”) values of the new images from those of theoriginal scan yields a color change profile. This is shown forn-butylamine in FIG. 4, in which color change profiles of themetalloporphyrin sensor array 16 as a function of exposure time ton-butylamine vapor. Subtraction of the initial scan from a scan after 5min. of N₂ exposure was used as a control, giving a black response, asshown. 9.3% n-butylamine in N₂ was then passed over the array and scansmade after exposure for 30 s, 5 min., and 15 min. The red, green andblue (“RGB”) mode images were subtracted (absolute value) to produce thecolor change profiles illustrated. Virtually all porphyrins aresaturated after 30 seconds of exposure, yielding a color fingerprintunique for each class of analytes, which is illustrated in FIG. 4.

[0056] More specifically, subtraction of the initial scan 40 from a scanafter 5 min. of N₂ exposure was used as a control, giving a blackresponse, as shown in FIG. 4. A nitrogen flow stream containing 0.093%n-butylamine was then passed over the array 16 and scans 42, 44, and 46were made after exposure for 30 seconds, 5 minutes, and 15 minutes,respectively. The RGB mode images were subtracted (absolute value) usingAdobe Photoshop™ (which comprises standard image analyzing software),with contrast enhancement by expanding the pixel range (a 32 value rangewas expanded to 256 each for the R, G, and B values). Subtraction ofexposed and unexposed images gives color change patterns that vary inhue and intensity. Because differentiation is provided by an array ofdetectors, the system has parallels the mammalian olfactory system. Asshown in FIG. 4 and summarized in Table 2 below, the dyes have thefollowing colors in scans 42, 44, and 46. TABLE 2 (Summarizing Colors ofDyes in FIG. 4, Scans 42, 44, and 46) Sn⁴⁺ — No Change Co³⁺ — Green Cr³⁺— Green Mn³⁺ — No Change Fe³⁺ — Red Co²⁺ — Faint Green Cu²⁺ — No ChangeRu²⁺ — No Change Zn²⁺ — Light Green Ag²⁺ — No Change 2H⁺ (Free Base“FB”) — Light Blue

[0057] As summarized in Table 3 below, for the TTP array 16 depicted onthe left-hand side of FIG. 4, the dyes have the following colors. TABLE3 Sn⁴⁺ — Greenish Yellow Co³⁺ — Red Cr³⁺ — Yellow with Dark Red CenterMn³⁺ — Greenish Yellow Fe³⁺ — Dark Red Co²⁺ — Red Cu²⁺ — Red Ru²⁺ —Light Yellow Zn²⁺ — Red Ag²⁺ — Red 2H⁺ (Free Base “FB”) — Red

EXAMPLE 2

[0058] Visible spectral shifts and absorption intensity differencesoccur upon ligation of the metal center, leading to readily observablecolor changes. As is well known to those with skill in the art, themagnitude of spectral shift correlates with the polarizability of theligand; hence, there exists an electronic basis for analyte distinction.Using metal centers that span a range of chemical hardness and ligandbinding affinity, a wide range of volatile analytes (including softligands, such as thiols, and harder ligands, such as amines) aredifferentiable. Because porphyrins have been shown to exhibit wavelengthand intensity changes in their absorption bands with varying solventpolarity, it is contemplated that the methods and apparatus of thepresent invention can be used to calorimetrically distinguish among aseries of weakly ligating solvent vapors (e.g., arenes, halocarbons, orketones), as shown for example in FIG. 5.

[0059] A comparison of color changes at saturation for a wide range ofanalytes is shown in FIG. 5. Each analyte is identified under thecolored array 16 that identifies each analyte.). DMF stands for theanalyte dimethylformamide, and THF stands for the analytetetrahydrofuran. As shown in FIG. 5 and summarized in Table 4 below, thecolors of each dye in response to a particular analyte are as follows.TABLE 4 Analyte: DMF Sn⁴⁺ — No Change Co³⁺ — Green Cr³⁺ — No Change Mn³⁺— No Change Fe³⁺ — No Change Co²⁺ — No Change Cu²⁺ — Blue Ru²⁺ — NoChange Zn²⁺ — No Change Ag²⁺ — No Change 2H⁺ (Free Base “FB”) — BlueAnalyte: Ethanol Sn⁴⁺ — Dark Blue Co³⁺ — No Change Cr³⁺ — Red Mn³⁺ — NoChange Fe³⁺ — No Change Co²⁺ — No Change Cu²⁺ — No Change Ru²⁺ — NoChange Zn²⁺ — Blue Ag²⁺ — No Change 2H⁺ (Free Base “FB”) - No ChangeAnalyte: Pyridine Sn⁴⁺ — No Change Co³⁺ — Green Cr³⁺ — Dark Green Mn³⁺ —No Change Fe³⁺ — No Change Co²⁺ — No Change Cu²⁺ — No Change Ru²⁺ — NoChange Zn²⁺ — Green Ag²⁺ — No Change 2H⁺ (Free Base “FB”) — BlueAnalyte: Hexylamine Sn⁴⁺ — No Change Co³⁺ — Dark Green Cr³⁺ — Green Mn³⁺— No Change Fe³⁺ — Red Co²⁺ — No Change Cu²⁺ — Blue Ru²⁺ — No ChangeZn²⁺ — Green Ag²⁺ — Dark Blue 2H⁺ (Free Base “FB”) — Blue Analyte:Acetonitrile Sn⁴⁺ — Blue Co³⁺ — Dark Green Cr³⁺ — No Change Mn³⁺ —Yellow Fe³⁺ — Dark Green Co²⁺ — No Change Cu²⁺ — Blue Ru²⁺ — Blue (faintdot) Zn²⁺ — Blue Ag²⁺ — No Change 2H⁺ (Free Base “FB”) — Blue Analyte:Acetone Sn⁴⁺ — No Change Co³⁺ — No Change Cr³⁺ — Red (small dot) Mn³⁺ —No Change Fe³⁺ — No Change Co²⁺ — No Change Cu²⁺ — Dark Blue Ru²⁺ — NoChange Zn²⁺ — Dark Blue Ag²⁺ — No Change 2H⁺ (Free Base “FB”) — BlueAnalyte: THF Sn⁴⁺ — Dark Blue Co³⁺ — Green Cr³⁺ — Red Mn³⁺ — Blue (smalldot) Fe³⁺ — Dark Green Co²⁺ — No Change Cu²⁺ — Blue Ru²⁺ — No ChangeZn²⁺ — Blue Ag²⁺ — No Change 2H⁺ (Free Base “FB”) — Blue Analyte: CH₂Cl₂Sn⁴⁺ — Dark Blue Co³⁺ — No Change Cr³⁺ — No Change Mn³⁺ — Yellow and Red(small Fe³⁺ — No Change Co²⁺ — No Change dot) Cu²⁺ — Dark Blue Ru²⁺ — NoChange Zn²⁺ — No Change Ag²⁺ — No Change 2H⁺ (Free Base “FB”) — BlueAnalyte: CHCl₃ Sn⁴⁺ — Dark Blue Co³⁺ — Dark Green Cr³⁺ — Yellow (circle)Mn³⁺ — Yellow Fe³⁺ — Dark Green (very faint) Co²⁺ — No Change Cu²⁺ —Dark Blue (very faint) Ru²⁺ — No Change Zn²⁺ — Blue Ag²⁺ — Blue (veryfaint) 2H⁺ (Free Base “FB”) — Blue Analyte: P(OC₂H₅)₃ Sn⁴⁺ — No ChangeCo³⁺ — Yellow Cr³⁺ — Dark Green Mn³⁺ — No Change Fe³⁺ — Dark Green (veryfaint) Co²⁺ — Greenish Yellow Cu²⁺ — Dark Blue (faint) Ru²⁺ — No ChangeZn²⁺ — Greenish Blue Ag²⁺ — Blue (very faint) 2H⁺ (Free Base “FB”) —Blue Analyte: P(C₄H₉)₃ Sn⁴⁺ — No Change Co³⁺ — Yellow and Red Cr³⁺ —Deep Red Mn³⁺ — No Change Fe³⁺ — Dark Green (faint) Co²⁺ — Red (withsome yellow) Cu²⁺ — No Change Ru²⁺ — Dark Blue Zn²⁺ — Yellow Ag²⁺ — NoChange 2H⁺ (Free Base “FB”) — No Change Analyte: C₆H₁₃SH Sn⁴⁺ — GreenCo³⁺ — No Change Cr³⁺ — Yellow circle surrounded by greenish blue circleMn³⁺ — Yellow Fe³⁺ — Dark Green Co²⁺ — No Change Cu²⁺ — Dark Blue(faint) Ru²⁺ — No Change Zn²⁺ — Green Ag²⁺ — Blue (very faint) 2H⁺ (FreeBase “FB”) — Blue Analyte: (C₃H₇)₂S Sn⁴⁺ — Dark Blue (faint) Co³⁺ — DeepGreen Cr³⁺ — Green Mn³⁺ — No Change Fe³⁺ — Dark Green Co²⁺ — Dark Green(very faint) Cu²⁺ — Dark Blue (faint) Ru²⁺ — Green Zn²⁺ — Green Ag²⁺ —Blue (very faint) 2H⁺ (Free Base “FB”) — Blue Analyte: Benzene Sn⁴⁺ — NoChange Co³⁺ — Green Cr³⁺ — Yellow (very faint) Mn³⁺ — Yellow (somegreen) Fe³⁺ — Dark Green Co²⁺ — No Change Cu²⁺ — No Change Ru²⁺ — NoChange Zn²⁺ — Dark Green Ag²⁺ — No Change 2H⁺ (Free Base “FB”) — Blue

[0060] The degree of ligand softness (roughly their polarizability)increases from left to right, top to bottom as shown in FIG. 1. Eachanalyte is easily distinguished from the others, and there are familyresemblances among chemically similar species (e.g., pyridine andn-hexylamine). Analyte distinction originates both in the metal-specificligation affinities and in their specific, unique color changes uponligation. Each analyte was delivered to the array as a nitrogen streamsaturated with the analyte vapor at 20° C. (to ensure completesaturation, 30 min. exposures to vapor were used. Although thesefingerprints were obtained by exposure to saturated vapors (thousands ofppm), unique patterns can be identified at much lower concentrations.

[0061] The metalloporphyrin array 16 has been used to quantify singleanalytes and to identify vapor mixtures. Because the images' colorchannel data (i.e., RGB values) vary linearly with porphyrinconcentration, we were able to quantify single porphyrin responses todifferent analytes. Color channel data were collected for individualspots and plotted, for example, as the quantity(R_(plt)−R_(spt))/(R_(plt)), where R_(plt) was the red channel value forthe initial silica surface and R_(spt) the average value for the spot.For example, Fe(TFPP)(Cl) responded linearly to octylamine between 0 and1.5 ppm. Other porphyrins showed linear response ranges that varied withligand affinity (i.e., equilibrium constant).

EXAMPLE 3

[0062] The array of the present invention has demonstrated interpretableand reversible responses even to analyte mixtures of strong ligands,such as pyridines and phosphites, as is shown in FIG. 6. Color changepatterns for the mixtures are distinct from either of the neat vapors.Good reversibility was demonstrated for this analyte pair as the vapormixtures were cycled between the neat analyte extremes, as shown in FIG.6, which shows the two component saturation responses to mixtures of2-methylpyridine (“2MEPY”) and trimethylphosphite (“TMP”). Vapormixtures were obtained by mixing the analyte-saturated N₂ streams atvariable flow ratios. A single plate was first exposed to puretrimethylphosphite vapor in N₂ (Scan A), followed by increasing molefractions of 2-methylpyridine up to pure 2-methylpyridine vapor (ScanC), followed by decreasing mole fractions of 2-methylpyridine back topure trimethylphosphite vapor. In both directions, scans were taken atthe same mole fraction trimethylphosphite and showed excellentreversibility; scans at mole fractions at 67% trimethylphosphite(χ_(tmp)==0.67, Scans B and D) and of their difference map are shown(Scan E). Response curves for the individual porphyrins allow forquantification of the mixture composition. The colors of each dye uponexposure to the analytes TMP and 2MEPY are shown in FIG. 6 and aresummarized in Table 5 below. TABLE 5 Scan A, Analyte: Neat TMP Sn⁴⁺ —Dark Blue Co³⁺ — Yellow Cr³⁺ — No Change Mn³⁺ — Yellow with red centerFe³⁺ — Dark Green Co²⁺ — Greenish Yellow Cu²⁺ — Dark Blue Ru²⁺ — NoChange Zn²⁺ — Blue Ag²⁺ — Green (very faint) 2H⁺ (Free Base “FB”) —Reddish Blue Scan B, Analyte: TMP,x_(TMP) = 0.67 Sn⁴⁺ — Blue Co³⁺ —Green Cr³⁺ — Green (small dot) Mn³⁺ — Yellow and Green Fe³⁺ — Green andYellow Co²⁺ — Green with red center Cu²⁺ — Dark Blue Ru²⁺ — Purple (veryfaint) Zn²⁺ — Blue Ag²⁺ — Greenish Blue 2H⁺ (Free Base “FB”) — ReddishBlue Scan C, Analyte: Neat 2MEPY Sn⁴⁺ — Blue Co³⁺ — Green Cr³⁺ — NoChange Mn³⁺ — Yellow and Green with Fe³⁺ — Red with some Yellow Co²⁺ —Green Red center Cu²⁺ — Dark Blue Ru²⁺ — Deep Blue Zn²⁺ — Green withsome Blue Ag²⁺ — Green with some Blue 2H⁺ (Free Base “FB”) — ReddishBlue Scan D, Analyte: TMP,x_(TMP) = 0.67 Sn⁴⁺ — Blue Co³⁺ — Green Cr³⁺ —No Change Mn³⁺ — Yellow and Green Fe³⁺ — Green and Yellow Co²⁺ — GreenCu²⁺ — Dark Blue Ru²⁺ — Purple (very faint) Zn²⁺ — Blue Ag²⁺ — GreenishBlue (very 2H⁺ (Free Base “FB”) — faint) Reddish Blue Scan E Sn⁴⁺ — NoChange Co³⁺ — No Change Cr³⁺ — No Change Mn³⁺ — No Change Fe³⁺ — NoChange Co²⁺ — No Change Cu²⁺ — Blue (very faint) Ru²⁺ — Blue (small dot)Zn²⁺ — No Change Ag²⁺ — Blue (very faint) 2H⁺ (Free Base “FB”) — Green

EXAMPLE 4

[0063] In an effort to understand the origin of the color changes uponvapor exposure, diffuse reflectance spectra were obtained for singleporphyrin spots before and after exposure to analyte vapors. Porphyrinsolutions were spotted in 50 μL aliquots onto a plate and allowed to dryunder vacuum at 50° C. Diffuse reflectance spectra of the plate werethen taken using a UV-visible spectrophotometer equipped with anintegrating sphere. Unique spectral shifts were observed upon analyteexposure, which correlated well with those seen from solution ligation.For example, Zn(TPP) exposure to ethanol and pyridine gave unique shiftswhich were very similar to those resulting from ligand exposure insolution. FIG. 7 shows a comparison of Zn(TPP) spectral shifts uponexposure to ethanol and pyridine (py) in methylene chloride solution (A)and on the reverse phase support (B). In both A and B, the bandscorrespond, from left to right, to Zn(TPP), Zn(TPP)(C₂H₅OH), andZn(TPP)(py), respectively. Solution spectra (A) were collected using aHitachi U-3300 spectrophotometer; Zn(TPP), C₂H₅OH, and py concentrationswere approximately 2 μM, 170 mM, and 200 μM, respectively. Diffusereflectance spectra (B) were obtained with an integrating sphereattachment before exposure to analytes, after exposure to ethanol vaporin N₂, and after exposure to pyridine vapor in N₂ for 30 min. each usingthe flow cell.

[0064] Improvement to Low Concentration Response

[0065] Color changes at levels as low as 460 ppb have been observed foroctylamine vapor, albeit with slow response times due to the highsurface area of the silica on the plate 18. The surface area of C2plates is ≈350 m²/gram. Removal of excess silica gel surrounding theporphyrin spots from the plate 18 led to substantial improvements inresponse time for exposures to trace levels of octylamine. Because thehigh surface area of the reverse phase silica surface is primarilyresponsible for the increased response time, other means of solidsupport or film formation can be used to improve low concentrationresponse.

[0066] Further, the present invention contemplates miniaturization ofthe array using small wells 60 (<1 mm), for example in glass, quartz, orpolymers, to hold metalloporphyrin or other dyes as thin films, whichare deposited as a solution, by liquid droplet dispersion (e.g.,airbrush or inkjet), or deposited as a solution of polymer withmetalloporphyrin.

[0067] These embodiments are depicted in FIGS. 8, 9, and 10. FIG. 8illustrates the interfacing of a microplate 60 into an assemblyconsisting of a CCD 70, a microplate 72 and a light source 74. FIG. 9illustrates another embodiment of the present invention, and moreparticularly, a microwell porphyrin array wellplate 80 constructed frompolydimethylsiloxane (PDMS). The colors of the dyes shown in FIG. 9 aresummarized below in Table 6. TABLE 6 Sn⁴⁺ — Dark Red Co³⁺ — Dark RedCr³⁺ — Dark Green Mn³⁺ — Green Fe³⁺ — Dark Red Co²⁺ — Yellowish GreenCu²⁺ — Deep Red Ru²⁺ — Dark Red Zn²⁺ — Red with some Yellow Ag²⁺ — Red2H⁺ (Free Base “FB”) — Red

[0068]FIG. 10 demonstrates deposition of metalloporphyrin/polymer(polystyrene/dibutylphthalate) solutions upon a plate, which includes aseries of micro-machined Teflon® posts 100 having the same basicposition relative to each other as shown in FIG. 2A and FIG. 2B. Thecolors for the dyes in the middle of FIG. 10 are summarized in Table 7below. TABLE 7 Sn⁴⁺ — Yellow Co³⁺ — Orange Cr³⁺ — Yellow Mn³⁺ — YellowFe³⁺ — Orange Co²⁺ — Orange Cu²⁺ — Orange Ru²⁺ — Dark Yellow Zn²⁺ —Orange Ag²⁺ — Orange 2H⁺ (Free Base “FB”) — Red

[0069] The colors for the dyes on the right hand side of FIG. 10 aresummarized in Table 8 below. TABLE 8 Sn⁴⁺ — No Change Co³⁺ — Green Cr³⁺— Red Mn³⁺ — Blue Fe³⁺ — Red Co²⁺ — Red, Green, Blue, and Yellow Cu²⁺ —Green with some Blue Ru²⁺ — Blue (very faint) Zn²⁺ — Yellow with someRed Ag²⁺ — Green with some Blue 2H⁺ (Free Base “FB”) — Green with someBlue

EXAMPLE 5

[0070]FIG. 11 shows the color profile changes from a microplate of thetype shown in FIG. 10. The microplate, consisting of a minimized arrayof four metalloporphyrins, i.e., Sn(TPP)(Cl₂), Co(TPP)(Cl), Zn(TPP),Fe(TFPP)(Cl), clockwise from the upper left (where TFPP stands for5,10,15,20-tetrakis(pentafluorophenyl)porphyrinate). The color profilechanges are shown in FIG. 11 after exposure to low levels ofn-octylamine, dodecanethiol (C₁₂H₂₅ SH), and tri-n-butylphosphine(P(C₄H₉)₃), each at 1.8 ppm, which is summarized in Table 9 below. TABLE9 Dyes on Teflon ® Sn — Dark Yellow Co — Red Zn — Red Fe — Orange withRed outline Dyes exposed to n-octylamine Sn — No Change Co — Green (veryfaint) Zn — Red Fe — Green Dyes exposed to C₁₂H₂₅SH Sn — Red Co — Greenwith some red, yellow and blue (faint) Zn — Red with some green andyellow Fe — Blue (very faint) Dyes exposed to P(C₄H₉)₃ Sn — No Change Co— Yellow with red center and some red periphery Zn — Green Fe — Yellowwith some Green and Blue

[0071] The low ppm levels of octylamine, an analyte of interest, weregenerated from temperature-regulated octylamine/dodecane solutions withthe assumption of solution ideality. The dodecane acts as a diluent tolower the level of octylamine vapor pressure for the purposes of thisdemonstration of the invention.

EXAMPLE 6

[0072]FIG. 12 illustrates the immunity of the present invention tointerference from water vapor. The hydrophobicity of the reverse phasesupport greatly any possible effects from varying water vapor in theatmosphere to be tested. For instance, as shown in FIG. 12, a colorfingerprint generated from exposure of the array to n-hexylamine (0.86%in N₂) was identical to that for n-hexylamine spiked heavily with watervapor (1.2% H₂O, 0.48% hexylamine in N₂). See scans 120, 122 and 124.The ability to easily detect species in the presence of a large waterbackground represents a substantial advantage over mass-sensitivesensing techniques or methodologies that employ polar polymers as partof the sensor array. The color patterns shown in FIG. 12 are summarizedin Table 10 below. TABLE 10 Scan 120 Sn⁴⁺ — No Change Co³⁺ — Green Cr³⁺— Green Mn³⁺ — No Change Fe³⁺ — Red Co²⁺ — No Change Cu²⁺ — No ChangeRu²⁺ — No Change Zn²⁺ — Green Ag²⁺ — No Change 2H⁺ (Free Base “FB”) —Dark Blue Scan 122 Sn⁴⁺ — No Change Co³⁺ — Green Cr³⁺ — Green Mn³⁺ — NoChange Fe³⁺ — Red Co²⁺ — No Change Cu²⁺ — No Change Ru²⁺ — Green (smalldot) Zn²⁺ — Green Ag²⁺ — No Change 2H⁺ (Free Base “FB”) — Dark Blue Scan124 Sn⁴⁺ — Bluish Circle Co³⁺ — Bluish Circle Cr³⁺ — Bluish Circle Mn³⁺— Bluish Circle Fe³⁺ — Bluish Circle Co²⁺ — Bluish Circle Cu²⁺ — BluishCircle Ru²⁺ — Bluish Circle Zn²⁺ — Bluish Circle Ag²⁺ — Bluish Circle2H⁺ (Free Base “FB”) — Bluish Circle

[0073] Additional Features of the Preferred Embodiments of the Invention

[0074] Having demonstrated electronic differentiation, an importantfurther goal is the shape-selective distinction of analytes (e.g.,n-hexylamine vs. cyclohexylamine). Functionalized metalloporphyrins thatlimit steric access to the metal ion are candidates for suchdifferentiation. For instance, we have been able to control ligation ofvarious nitrogenous ligands to dendrimer-metalloporphyrins and induceselectivities over a range of more than 10⁴. As an initial attempttoward shape-selective detection, we employed the slightly-hinderedtetrakis(2,4,6-trimethoxyphenyl)porphyrins (TTMPP) in our sensing array.With these porphyrins, fingerprints for t-butylamine and n-butylamineshowed subtle distinctions, as did those for cyclohexylamine andn-hexylamine. Using more hindered metalloporphyrins, it is contemplatedthat the present invention can provide greater visual differentiation.Such porphyrins include those whose periphery is decorated withdendrimer, siloxyl, phenyl, t-butyl and other bulky substituents,providing sterically constrained pockets on at least one face (andpreferably both) of the porphyrin.

[0075] In a similar fashion, it is contemplated that the sensor platesof the present invention can be used for the detection of analytes inliquids or solutions, or solids. A device that detects an analyte in aliquid or solution or solid can be referred to as an artificial tongue.Proper choice of the metal complexes and the solid support must precludetheir dissolution into the solution to be analyzed. It is preferred thatthe surface support repel any carrier solvent to promote the detectionof trace analytes in solution; for example, for analysis of aqueoussolutions, reverse phase silica has advantages as a support since itwill not be wetted directly by water.

[0076] Alternative sensors in accordance with the present invention mayinclude any other dyes or metal complexes with intense absorbance in theultraviolet, visible, or near infrared spectra that show a color changeupon exposure to analytes. These alternative sensors include, but arenot limited to, a variety of macrocycles and non-macrocycles such aschlorins and chlorophylls, phthalocyanines and metallophthalocyanines,salen-type compounds and their metal complexes, or othermetal-containing dyes.

[0077] The present invention can be used to detect a wide variety ofanalytes regardless of physical form of the analytes. That is, thepresent invention can be used to detect any vapor emitting substance,including liquid, solid, or gaseous forms, and even when mixed withother vapor emitting substances, such solution mixtures of substances.

[0078] The present invention can be used in combinatorial libraries ofmetalloporphyrins for shape selective detection of substrates where thesubstituents on the periphery of the macrocycle or the metal bound bythe porphyrin are created and then physically dispersed in twodimensions by (partial) chromatographic or electrophoretic separation.

[0079] The present invention can be used with chiral substituents on theperiphery of the macrocycle for identification of chiral substrates,including but not limited to drugs, natural products, blood or bodilyfluid components.

[0080] The present invention can be used for analysis of biologicalentities based on the surface proteins, oligosacharides, antigens, etc.,that interact with the metalloporphyrin array sensors of the presentinvention. Further, the sensors of the present invention can be used forspecific recognition of individual species of bacteria or viruses.

[0081] The present invention can be used for analysis of nucleic acidsequences based on sequence specific the surface interactions with themetalloporphyrin array sensors. The sensors of the present invention canbe used for specific recognition of individual sequences of nucleicacids. Substituents on the porphyrins that would be particularly usefulin this regard are known DNA intercalating molecules and nucleic acidoligomers.

[0082] The present invention can be used with ordinary flat bedscanners, as well as portable miniaturized detectors, such as CCDdetectors with microarrays of dyes such as metalloporphyrins.

[0083] The present invention can be used for improved sensitivity,automation of pattern recognition of liquids and solutions, and analysisof biological and biochemical samples.

[0084] Superstructure Bonded to the Periphery of the Porphyrin

[0085] The present invention includes modified porphyrins that have asuper structure bonded to the periphery of the porphyrin. A superstructure bonded to the periphery of the porphyrin in accordance withthe present invention includes any additional structural element orchemical structure built at the edge of the porphyrin and bondedthereto.

[0086] The super structures can include any structural element orchemical structure characterized in having a certain selectivity. Thoseof skill in the art will recognize that the super structures of thepresent invention include structures that are shape selective, polarityselective, inantio selective, regio selective, hydrogen bondingselective, and acid-base selective. This structures can includesiloxyl-substituted substituents, nonsiloxyl-substituted substituentsand nonsiloxyl-substituted substituents, including but not limited toaryl substituents, alkyl substituents, and organic, organometallic, andinorganic functional group substituents.

[0087] Superstructure Bis-Pocket Porphyrins

[0088] A number of modified porphyrins have been synthesized to mimicvarious aspects of the enzymatic functions of heme proteins, especiallyoxygen binding (myoglobin and hemoglobin) and substrate oxidation(cytochrome P-450). See Suslick, K. S.; Reinert, T. J. J. Chem. Ed.1985, 62, 974; Collman, J. P.; Zhang, X.; Lee, V. J.; Uffelman, E. S.;Brauman, J. I. Science 1993,261, 1404; Collman, J. P.; Zhang, X. inComprehensive Supramolecular Chemistry; Atwood, J. L.; Davies, J. E. D.;MacNicol, D. D.; Vogtel, F. Eds.; Pergamon: New York, 1996; vol. 5, pp.1-32; Suslick, K. S.; van Deusen-Jeffries, S. in ComprehensiveSupramolecular Chemistry; Atwood, J. L.; Davies, J. E. D.; MacNicol, D.D.; Vogtel, F. Eds.; Pergamon: New York, 1996; vol. 5, pp. 141-170;Suslick, K. S. in Activation and Functionalization of Alkanes; Hill, C.L., ed.; Wiley & Sons: New York, 1989; pp. 219-241. The notable propertyof many heme proteins is their remarkable substrate selectivity; thedevelopment of highly regioselective synthetic catalysts, however, isstill at an early stage. Discrimination of one site on a molecule fromanother and distinguishing among many similar molecules presents adifficult and important challenge to both industrial and biologicalchemistry. See Metalloporphyrins in Catalytic Oxidations; Sheldon, R. A.Ed. Marcel Dekker: New York, 1994). Although the axial ligationproperties of simple synthetic metalloporphyrins are well documented inliterature, see Bampos, N.; Marvaud, V.; Sanders, J. K. M. Chem. Eur. J.1998, 4, 325; Stibrany, R. T.; Vasudevan, J.; Knapp, S.; Potenza, J. A.;Emge, T.; Schugar, H. J. J. Am. Chem. Soc. 1996, 118, 3980, size andshape control of ligation to peripherally modified metalloporphyrins hasbeen largely unexplored, with few notable exceptions, where only limitedselectivities have been observed. See Bhyrappa, P.; Vaijayanthimala, G.;Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262; Imai, H.; Nakagawa, S.;Kyuno, E. J. Am. Chem. Soc. 1992, 114, 6719.

[0089] The present invention includes the synthesis, characterizationand remarkable shape-selective ligation of silylether-metalloporphyrinscaffolds derived from the reaction of5,10,15,20-tetrakis(2′,6′-dihydroxyphenyl)porphyrinatozinc(II) witht-butyldimethylsilyl chloride, whereby the two faces of the Zn(II)porphyrin were protected with six, seven, or eight siloxyl groups. Thisresults in a set of three porphyrins of nearly similar electronics butwith different steric encumbrance around central metal atom present inthe porphyrin. Ligation to Zn by classes of different sized ligandsreveal shape selectivities as large as 10⁷.

[0090] A family of siloxyl-substituted bis-pocket porphyrins wereprepared according to the scheme of FIG. 13. The abbreviations of theporhyrins that can be made in accordance with the scheme shown in FIG.13 are as follows:

[0091] Zn(TPP), 5,10,15,20-tetraphenylporphyrinatozinc(II);

[0092] Zn[(OH)₆PP],5-phenyl-10,15,20-tris(2′,6′-dihydroxyphenyl)porphyrinatozinc(II);

[0093] Zn[(OH)₈PP],5,10,15,20-tetrakis(2′,6′-dihydroxyphenyl)porphyrinatozinc(II);

[0094] Zn(Si₆PP),5(phenyl)-10,15,20-trikis(2′,6′-disilyloxyphenyl)porphyrinatozinc(II);

[0095] Zn(Si₇OHPP),5,10,15-trikis(2′,6′-disilyloxyphenyl)-20-(2′-hydroxy-6′-silyloxyphenyl)porphyrinatozinc(II);

[0096] Zn(Si₈PP),5,10,15,20-tetrakis(2′,6′-disilyloxyphenyl)porphyrinatozinc(II). Thesynthesis of Zn[(OH)₆PP], Zn(Si₆PP), and Zn(Si₈PP) is detailed below.Zn[(OH)₆PP] and Zn[(OH)₈PP] were obtained (see Bhyrappa, P.;Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262)from demethylation (see Momenteau, M.; Mispelter, J.; Loock, B.;Bisagni, E. J. Chem. Soc. Perkin Trans. 1, 1983, 189) of correspondingfree base methoxy compounds followed by zinc(II) insertion. The methoxyporphyrins were synthesized by acid catalysed condensation of pyrrolewith respective benzaldehydes following Lindsey procedures. See Lindsey,J. S.; Wagner, R. W. J. Org. Chem. 1989, 54, 828. Metalation was done inmethanol with Zn(O₂CCH₃)₂. The t-butyldimethylsilyl groups wereincorporated into the metalloporphyrin by stirring a DMF solution ofhydroxyporphyrin complex with TBDMSiCl (i.e., t-butyldimethylsilylchloride) in presence of imidazole. See Corey, E. J; Venkateswarlu, A.J. Am. Chem. Soc. 1972, 94, 6190. The octa (Zn(Si₈PP)), hepta(Zn(Si₇OHPP)), and hexa (Zn(Si₆PP)) silylether porphyrins were obtainedfrom Zn[(OH)₈PP] and Zn[(OH)₆PP], respectively. The compounds werepurified by silica gel column chromatography and fully characterized byUV-Visible, ¹H-NMR, HPLC, and MALDI-TOF MS.

[0097] The size and shape selectivities of the binding sites of thesebis-pocket Zn silylether porphyrins were probed using the axial ligationof various nitrogenous bases of different shapes and sizes in toluene at25° C. Zn(II) porphyrins were chosen because, in solution, theygenerally bind only a single axial ligand. Successive addition of ligandto the porphyrin solutions caused a red-shift of the Soret band typicalof coordination to zinc porphyrin complexes. There is no evidence fromthe electronic spectra of these porphyrins for significant distortionsof the electronic structure of the porphyrin. The binding constants(K_(eq)) and binding composition (always 1:1) were evaluated usingstandard procedures. See Collman, J. P.; Brauman, J. I.; Doxsee, K. M.;Halbert, T. R.; Hayes, S. E.; Suslick, K. S. J. Am. Chem. Soc. 1978,100, 2761; Suslick, K. S.; Fox, M. M.; Reinert, T. J. Am. Chem. Soc.1984, 106,4522. The K_(eq) values of the silylether porphyrins withnitrogenous bases of different classes are compared with the stericallyundemanding Zn(TPP) in FIGS. 14a, 14 b, and 14 c. It is worth noting theparallel between shape selectivity in these equilibrium measurements andprior kinetically-controlled epoxidation and hydroxylation. See Collman,J. P.; Zhang, X. in Comprehensive Supramolecular Chemistry; Atwood, J.L.; Davies, J. E. D.; MacNicol, D. D.; Vogtel, F. Eds.; Pergamon: NewYork, 1996; vol. 5, pp. 1-32; Suslick, K. S.; van Deusen-Jeffries, S. inComprehensive Supramolecular Chemistry; Atwood, J. L.; Davies, J. E. D.;MacNicol, D. D.; Vogtel, F. Eds.; Pergamon: New York, 1996; vol. 5, pp.141-170; Suslick, K. S. in Activation and Functionalization of Alkanes;Hill, C. L., ed.; Wiley & Sons: New York, 1989; pp. 219-241; Bhyrappa,P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc., 1996,118, 5708-5711. Suslick, K. S.; Cook, B. R. J. Chem. Soc., Chem. Comm.1987,200-202; Cook, B. R.; Reinert, T. J.; Suslick, K. S. J. Am. Chem.Soc. 1986,108,7281-7286; Suslick, K. S.; Cook, B. R.; Fox, M. M. J.Chem. Soc., Chem. Commun. 1985, 580-582. The selectivity forequilibrated ligation appears to be substantially larger than forirreversible oxidations of similarly shaped substrates.

[0098] The binding constants of silylether porphyrins are remarkablysensitive to the shape and size of the substrates relative to Zn(TPP).See FIGS. 14a, 14 b, and 14 c. The binding constants of different aminescould be controlled over a range of 10¹ to 10⁷ relative to Zn(TPP). Itis believed that these selectivities originate from strong stericrepulsions created by the methyl groups of the t-butyldimethylsiloxylsubstituents. The steric congestion caused by these bulky silylethergroups is pronounced even for linear amines and small cyclic amines(e.g., azetidine and pyrrolidine).

[0099] There are very large differences in K_(eq) for porphyrins havingthree versus four silylether groups on each face (e.g., hexa- vs.octa-silylether porphyrins), as expected based on obvious stericarguments (see FIGS. 14a, 14 b, and 14 c). Even between the hexa- overhepta-silylether porphyrins, however, there are still substantialdifferences in binding behavior. It is believed that this is probablydue to doming of the macrocycle in the hexa- and hepta-silyletherporphyrins, which lessens the steric constraint relative to theoctasilylether porphyrin. Such doming will be especially important inporphyrins whose two faces are not identical. The free hydroxyfunctionality of the hepta-silylether may play a role in binding ofbi-functionalized ligands (e.g., free amino acids); for the simpleamines presented here, however, we have no evidence of any specialeffects.

[0100] These silylether porphyrins showed remarkable selectivities fornormal, linear amines over their cyclic analogues. For a series oflinear amines (n-propylamine through n-decylamine), K_(eq) were verysimilar for each of the silylether porphyrins. In comparison, therelative K_(eq) for linear versus cyclic primary amines (FIG. 14a,n-butylamine vs. cyclohexylamine) were significantly different: K_(eq)^(linear)/K_(eq) ^(cyclic) ranges from 1 to 23 to 115 to >200 forZn(TPP), Zn(Si₆PP), Zn(Si₇OHPP), and Zn(Si₈PP), respectively. Theability to discriminate between linear and cyclic compounds is thusestablished.

[0101] A series of cyclic 2° amines (FIG. 14b) demonstrate theremarkable size and shape selectivities of this family of bis-pocketporphyrins. Whereas the binding constants to Zn(TPP) with those aminesare virtually similar. In contrast, the K_(eq) values for silyletherporphyrins strongly depend on the ring size and its peripheralsubstituents. The effect of these shape-selective binding sites isclear, even for compact aromatic ligands with non-ortho methylsubstituents (FIG. 14c).

[0102] The molecular structures of these silylether porphyrins explainstheir ligation selectivity. The x-ray single crystal structure ofZn(Si₈PP) has been solved in the triclinic P1bar space group. See Singlecrystal x-ray structure of Zn(Si₈PP) shown in FIG. 15. As shown in FIG.15, Zn(Si₆PP) (energy minimized molecular model) and Zn(Si₈PP) (singlecrystal x-ray structure) have dramatically different binding pockets. Inthe octasilylether porphyrin, the top access on both faces of theporphyrin is very tightly controlled by the siloxyl pocket. In contrast,the metal center of the hexasilylether porphyrin is considerably moreexposed for ligation.

[0103]FIG. 15 illustrates molecular models of Zn(Si₆PP) (left column)and Zn(Si₈PP) (right column). The pairs of images from top to bottom arecylinder side-views, side-views, and top-views, respectively; spacefilling shown at 70% van der Waals radii; with the porphyrin carbonatoms shown in purple, oxygen atoms shown in red, silicon atoms ingreen, and Zn in dark red. The x-ray single crystal structure ofZn(Si₈PP) is shown; for Zn(Si₆PP), an energy-minimized structure wasobtained using Cerius 2 from MSI.

[0104] In summary, a series of bis-pocket siloxyl metalloporphyrincomplexes were prepared with sterically restrictive binding pockets onboth faces of the macrocycle. Ligation to Zn by various nitrogenousbases of different sizes and shapes were investigated. Shapeselectivities as large as 10⁷ were found, compared to unhinderedmetalloporphyrins. Fine-tuning of ligation properties of theseporphyrins was also possible using pockets of varying steric demands.The shape selectivities shown here rival or surpass those of anybiological system.

[0105] Examples of Synthesis of Super Structures

[0106] Synthesis of5-phenyl-10,15,20-tris(2′,6′-dihydroxy-phenyl)-porphyrinatozinc(II),Zn[(OH)₆PP]:

[0107] The free base5-phenyl-10,15,20-tris(2′,6′-dimethoxyphenyl)-porphyrin was synthesizedby Lewis acid catalyzed condensation of 2,6-dimethoxybezaldehyde andbenzaldehyde with pyrrole (3:1:4 mole ratio) following the Lindseyprocedure. See Lindsey, J. S.; Wagner, R. W. J. Org. Chem. 1989, 54,828. The mixture of products thus formed was purified by silica gelcolumn chromatography (if necessary, using CH₂Cl₂ as eluant). Theisolated yield of the desired product was found to be 7%(wrt pyrroleused). The corresponding hydroxyporphyrins were obtained bydemethylation with pyridine hydrochloride. See Momenteau, M.; Mispelter,J.; Loock, B.; Bisagni, E. J. Chem. Soc. Perkin Trans. 1, 1983, 189.After typical work-up known to those skilled in the art, the crudecompound was purified by silica gel column chromatography usingethylacetate as eluant. The first fraction was Zn[(OH)₆PP], which wascollected and the solvent was removed. The yield of the product was 90%(based on starting hydroxyporphryin). ¹H NMR of H₂[(OH)₆PP] inacetone-d₆ (ppm): 8.96-8.79(m, 8H, b-pyrrole H), 8.24(m, 2H, o-H5-Phenyl), 8.07 and 8.02(2s, 6H, —OH), 7.83(m, 3H, m,p-H 5-Phenyl),7.50(t, 3H, p-H hydroxyphenyl), 6.90(d, 6H, m-H hydroxyphenyl), −2.69(s,2H, imino-H). Elemental analysis, calcd. for C₄₄H₃₀O₆N₄.H₂O: C=72.5,H=4.4 and N=7.7%. Found C=72.7, H=4.4 and N=7.4%. The compound showedmolecular ion peak at 711 (m/z calcd. for C₄₄H₃₀O₆N₄=710) in FAB-MS.

[0108] The Zn derivative was obtain by stirring methanol solution ofH₂[(OH)₆PP] with excess Zn(O₂CCH₃)₂2H₂O for 1 hour. Methanol wasevaporated to dryness and the residue was dissolved in ethylacetate,washed with water, and the organic layer passed through anhyd. Na₂SO₄.The concentrated ethylacetate solution was passed through a silica gelcolumn and the first band was collected as the desired product. Theyield of the product was nearly quantitative. ¹H NMR of Zn(OH)₆PP inacetone-d₆ (ppm): 8.95-8.79(m, 8H, b-pyrrole H), 8.22(m, 2H, o-H5-Phenyl), 7.79(m, 3H, m,p-H 5-Phenyl), 7.75 and 7.65(2s, 6H, —OH),7.48(t, 3H,p-H hydroxyphenyl), 6.88(d, 6H, m-H hydroxyphenyl). Elementalanalysis, calcd. for ZnC₄₄H₂₈O₆N₄.H₂O: C=66.7, H=3.8, N=7.1 and Zn=8.3%.Found C=66.4, H=3.8, N=6.7 and Zn=8.2%. The compound showed molecularion peak at 774 (m/z calcd. for ZnC₄₄H₂₈O₆N₄=773) in FAB-MS.

[0109] Synthesis of5-phenyl-10,15,20-tris(2′,6′-disilyloxyphenyl)-porphyrinatozinc(II),Zn(Si₆PP):

[0110] The hexasilylether porphyrin was synthesized by stirring a DMFsolution of5-phenyl-10,15,20-tris(2′,6′-dihydroxyphenyl)-porphyrinatozinc(II) (100mg, 0.13 mmol) with t-butyldimethyl silylchloride (1.18 g, 7.8 mmol) inpresence of imidazole (1.2 g, 17.9 mmol) at 60° C. for 24 h undernitrogen. After this period the reaction mixture was washed with waterand extracted in CHCl₃. The organic layer was dried over anhyd. Na₂SO₄.The crude reaction mixture was loaded on a short silica gel column andeluted with mixture of CHCl₃/petether (1:1, v/v) to get rid of unreactedstarting material and lower silylated products. The desired compound wasfurther purified by running another silica gel column chromatographyusing mixture of CHCl₃/petether (1:3, v/v) as eluant. The yield of theproduct was 60% based on starting hydroxyporphyrin.

[0111]¹H NMR in chloroform-d (ppm): 8.94-8.82(m, 8H, b-pyrrole H),8.20(m, 2H, o-H 5-Phenyl), 7.74(m, 3H, m,p-H 5-Phenyl), 7.49(t, 3H, p-Hhydroxyphenyl), 6.91(t, 6H, m —H hydroxyphenyl), −0.02 and −0.34(2s,54H, t-butyl H), −0.43, −0.78 and −1.01(3s, 36H, methyl H). Elementalanalysis, calcd. for ZnC₈₀H₁₁₂O₆N₄Si₆: C=65.8, H=7.7, N=3.8, Si=11.5 andZn=4.5%. Found C=65.5, H=7.7, N=3.8, Si=11.2 and Zn=4.4%. The lowresolution MALDI-TOF mass spectrum showed molecular ion peak at 1457(m/z calcd. for ZnC₈₀H₁₁₂O₆N₄Si₆=1458).

[0112] Synthesis of5,10,15-tris(2′,6′-disilyoxyphenyl)-20-(2′-hydr-oxy-6′-silyloxyphenyl)porphyrinatozinc(II),[Zn(Si₇OHPP)], and5,10,15,20-tetrakis(2′,6′-disilyloxyphenyl)porphy-rinato-zinc(II),[Zn(Si₈PP)]:

[0113] The synthesis of precursor porphyrin5,10,15,20-tetrakis-(2′,6′-dihydroxyphenyl)porphyrin and its Znderivative was accomplished as reported earlier. See Bhyrappa, P.;Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem. Soc. 1999, 121, 262.The hepta-and octa-silylether porphyrins were synthesized by stirringDMF solution of5,10,15,20-tetrakis(2′,6′-dihydroxyphenyl)porphyrinatozinc(II) (100 mg,0.12 mmol) with t-butyldimethyl silylchloride (1.45 g, 9.6 mmol) inpresence of imidazole (1.50 g, 22.1 mmol) at 60° C. for 24 h undernitrogen. After usual work-up the mixture of crude products were loadedon a silica gel column and eluted with mixture of CHCl₃/pet. ether (1:1,v/v) to remove unreacted starting material and lower silylated products.The major product isolated from this column is a mixture of hepta- andocta-silylated porphyrins. The mixture thus obtained was furtherpurified by another silica gel column chromatography using mixture ofCHCl₃/pet. ether (1:3, v/v) as eluant. The first two bands were isolatedas octa- and hepta-silylether porphyrin at 45% and 30% yield,respectively. Both the compounds were characterized by UV-Visible, ¹HNMR and MALDI-TOF spectroscopic techniques. The homogeneity of thesample was verified by HPLC.

[0114] For Zn(Si₇OHPP), ¹H NMR in chloroform-d (ppm): 8.91(m, 8H,b-pyrrole H), 7.50(m, 4H, p-H), 7.01-6.81(m, 8H, m-H), 0.11 to−0.03(12s, 105H, t-butyl and methyl H). Elemental analysis, calcd. forZnC₈₆H₁₂₆O₈N₄Si₇: C=64.3, H=7.8, N=3.5, Si=12.3 and Zn=4.1%. FoundC=63.6, H=8.1, N=3.5, Si=12.1 and Zn=3.9%. The low resolution MALDI-TOFmass spectrum showed molecular ion peak at 1604 (m/z calcd. forZnC₈₆H₁₂₆O₈N₄Si₇=1604).

[0115] For Zn(Si₈PP), ¹H NMR in chloroform-d (ppm): 8.89(s, 8H,b-pyrrole H), 7.49(t, 4H, p-H), 6.92(d, 8H, m-H), 0.09(s, 72H, t-butylH), −1.01(s, 48H, methyl H). Elemental analysis, calcd. forZnC₉₂H₁₄₀O₈N₄Si₈: C=64.2, H=8.1, N=3.3, Si=13.1 and Zn=3.8%. FoundC=63.5, H=8.4, N=3.3, Si=12.8 and Zn=4.0%. The low resolution MALDI-TOFmass spectrum showed molecular ion peak at 1719 (m/z calcd. forZnC₉₂H₁₄₀O₈N₄Si₈=1718).

[0116] Additional Features of the Preferred Embodiments of the Invention

[0117] Having demonstrated electronic differentiation andshape-selective distinction of analytes that bind to metal ions inmetallodyes, an important further goal is the differentiation ofanalytes that do not bind or bind only weakly to metal ions. Suchanalytes include acidic compounds, such as carboxylic acids, and certainorganic compounds lacking ligatable functionality, such as simplealkanes, arenes, some alkenes and alkynes (especially if stericallyhindered), and molecules sterically hindered as to preclude effectiveligation. One approach that has been developed to achieve this goal inaccordance with the present invention is to include in the sensor arrayother chemoresponsive dyes, including pH sensitive dyes (i.e., pHindicator or acid-base indicator dyes that change color upon exposure toacids or bases), and/or solvatochromic dyes (i.e., dyes that changecolor depending upon the local polarity of their micro-environment).

[0118] It has been discovered that the addition of pH sensitive dyes andsolvatochromic dyes to other arrays containing metalloporphyrins asdescribed above expands the range of analytes to which the arrays aresensitive, improves sensitivities to some analytes, and increases theability to discriminate between analytes.

[0119] The present invention includes an artificial nose comprising anarray, the array comprising at least a first dye and a second dyedeposited directly onto a single support in a predetermined patterncombination, the combination of the dyes in the array having a distinctand direct spectral absorbance or reflectance response to an analytewherein the first dye and the second dye are selected from the groupconsisting of chemoresponsive dyes, and the second dye is distinct fromthe first dye. In a preferred embodiment, the first dye is selected fromthe group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine,and salen and their metal complexes. In another preferred embodiment,the second dye is selected from the group of dyes consisting ofacid-base indicator dyes and solvatochromic dyes.

[0120] The present invention includes a method of detecting an analytecomprising the steps of: (a) forming an array of at least a first dyeand a second dye deposited directly onto a single support in apredetermined pattern combination, the combination of the dyes in thearray having a distinct and direct spectral absorbance or reflectanceresponse to an analyte wherein the first dye and the second dye areselected from the group consisting of chemoresponsive dyes, and thesecond dye is distinct from the first dye; (b) subjecting the array toan analyte; (c) inspecting the array for a distinct and direct spectralabsorbance or reflectance response; and (d) correlating the distinct anddirect spectral response to the presence of the analyte. In a preferredmethod, the first dye is selected from the group consisting ofporphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and theirmetal complexes. In another preferred method, the second dye is selectedfrom the group of acid-base indicator dyes and solvatochromic dyes.

[0121] The present invention includes an artificial tongue comprising anarray, the array comprising at least a first dye and a second dyedeposited directly onto a single support in a predetermined patterncombination, the combination of the dyes in the array having a distinctand direct spectral absorbance or reflectance response to an analytewherein the first dye and the second dye are selected from the groupconsisting of chemoresponsive dyes, and the second dye is distinct fromthe first dye. In a preferred embodiment, the first dye is selected fromthe group consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine,and salen and their metal complexes. In another preferred embodiment,the second dye is selected from the group of dyes consisting ofacid-base indicator dyes and solvatochromic dyes.

[0122] Chemoresponsive dyes are those dyes that change color, in eitherreflected or absorbed light, upon changes in their chemical environment.Three general classes of chemoresponsive dyes are (1) Lewis acid/basedyes, (2) pH indicator dyes, and (3) solvatochromic dyes.

[0123] Lewis acid/base dyes are those dyes that contain a Lewis acidicor basic center (where a Lewis acid is an electron pair acceptor and aLewis base is an electron pair donor) and change color in response tochanges in the Lewis acidity or basicity of their environment. Aspecific set of Lewis acid/base dyes includes dyes such as porphyrin,chlorin, chlorophyll, phtahlocyanine, and salen and their metalcomplexes.

[0124] pH indicator or acid-base indicator dyes are those that changecolor in response to changes in the proton acidity or basicity (alsocalled Bronsted acidity or basicity) of their environment. A specificset of pH indicator dyes include Chlorphenol Red, Bromocresol Green,Bromocresol Purple, Bromothymol Blue, Phenol Red, Thymol Blue, CresolRed, Alizarin, Mordant Orange, Methyl Orange, Methyl Red, Congo Red,Victoria Blue B, Eosin Blue, Fat Brown B, Benzopurpurin 4B, Phloxine B,Orange G, Metanil Yellow, Naphthol Green B, Methylene Blue, Safranine O,Methylene Violet 3RAX, Sudan Orange G, Morin Hydrate, Neutral Red,Disperse Orange 25, Rosolic Acid, Fat Brown RR, Cyanidin chloride,3,6-Acridineamine, 6′-Butoxy-2,6-diamino-3,3′-azodipyridine,para-Rosaniline Base, Acridine Orange Base, Crystal Violet, andMalachite Green Carbinol Base.

[0125] Solvatochromic dyes are those that change color in response tochanges in the general polarity of their environment, primarily throughstrong dipole-dipole interactions. To some extent, all dyes inherentlyare solvatochromic, although some are much more responsive than others.A specific set of highly responsive solvatochromic dyes includeReichardt's Dye and Nile Red.

[0126] It has been discovered that the following pH indicator (i.e.,acid-base indicator) dyes and solvatochromic dyes are useful to expandthe range of analytes to which the arrays containing metalloporphyrinsare sensitive, improve sensitivities to some analytes, and increase theability to discriminate between analytes. Those skilled in the art willrecognize that other modifications and variations in the choice of suchauxiliary dyes may be made in addition to those described andillustrated herein without departing from the spirit and scope of thepresent invention. Accordingly, the choice of dyes described andillustrated herein should be understood to be illustrative only and notlimiting upon the scope of the present invention.

[0127] Chlorphenol Red

[0128] Molecular Formula: C₁₉H₁₂Cl₂O₅S

[0129] Molecular Weight: 423.28

[0130] CAS: 4430-20-0

[0131] Transition interval: pH 4.8 (yellow) to pH 6.7 (violet)

[0132] Bromocresol Green

[0133] Synonyms: 3′,3″,5′,5″Tetrabromo-m-cresolsulfonphthalein;Bromcresol Green

[0134] Molecular Formula: C₂₁H₁₄Br₄O₅S

[0135] Molecular Weight: 698.04

[0136] CAS: 76-60-8 $\begin{matrix}{{pH} = {3.8\quad {yellow}}} \\{= {5.4\quad {blue}}}\end{matrix}$

[0137] Bromocresol Purple

[0138] Synonyms: 5′,5″ dibromo-m-cresolsulfonphthalein; BromcresolPurple

[0139] Molecular Formula: C₂₁H₁₆Br₂O₅S

[0140] Molecular Weight: 698.04

[0141] CAS: 115-40-2 $\begin{matrix}{{pH} = {5.2\quad {yellow}}} \\{= {6.8\quad {blue}}}\end{matrix}$

[0142] Bromothymol Blue

[0143] Synonyms: 3′,3″-Dibromothymolsulfonphthalein; Bromthymol Blue

[0144] Molecular Formula: C₂₇H₂₈Br₂O₅S

[0145] Molecular Weight: 624.41

[0146] CAS: 76-59-5 $\begin{matrix}{{pH} = {6.0\quad {yellow}}} \\{= {7.6\quad {blue}}}\end{matrix}$

[0147] Phenol Red

[0148] Synonyms: Phenolsulfonphthalein

[0149] Molecular Formula: C₁₉H₁₄O₅S

[0150] Molecular Weight: 354.38

[0151] CAS: 143-74-8 $\begin{matrix}{{pH} = {6.8\quad {yellow}}} \\{= {8.2\quad {red}}}\end{matrix}$

[0152] Thymol Blue

[0153] Synonyms: Thymolsulfonphthalein

[0154] Molecular Formula: C₂₇H₃₀O₅S

[0155] Molecular Weight: 466.60

[0156] CAS: 76-61-9 $\begin{matrix}{{pH} = {1.2\quad {red}}} \\{= {2.8\quad {yellow}}} \\{= {8\quad {yellow}}} \\{= {9.2\quad {blue}}}\end{matrix}$

[0157] Cresol Red

[0158] Synonyms: Phenol,4,4′-(1,1-dioxido-3H-2,1-benzoxathiol-3-ylidene)bis[2-methyl-(9CI)]

[0159] Molecular Formula: C₂₁H₁₈O₅S

[0160] Molecular Weight: 382.43

[0161] CAS: 1733-12-6

[0162] pH 1.8 (orange) to pH 2.0 (yellow); Transition interval(alkaline): pH 7.0 (yellow) to pH 8.8 (violet)

[0163] Alizarin

[0164] Synonyms: 1,2-Dihydroxyanthraquinone, 9,10-Anthracenedione,1,2-dihydroxy-(9CI)

[0165] Molecular Formula: C₁₄H₈O₄

[0166] Molecular Weight: 240.22 ${pH}\begin{matrix}{= {5.5\quad {yellow}}} \\{= {6.8\quad {red}}} \\{= {10.1\quad {red}}} \\{= {12.1\quad {violet}}}\end{matrix}$

[0167] Mordant Orange 1

[0168] Synonyms: Alizarin Yellow R, C.I. 14030,5-(4-nitrophenylazo)salicylic acid

[0169] Molecular Formula: C₁₃H₉N₃O₅

[0170] Molecular Weight: 287.23

[0171] CAS: 2243-76-7

[0172] Methyl Orange

[0173] Synonyms: 4-(p-[Dimethylamino]phenylazo)benzenesulfonic acid,sodium salt Acid Orange 52

[0174] Molecular Formula: C₁₄H₁₄N₃O₃SNa

[0175] Molecular Weight: 327.3

[0176] pH 3.0 (pink)—pH 4.4 (yellow)

[0177] Methyl Red

[0178] Synonyms: 4-Dimethylaminoazobenzene-2′carboxylicacid;2-(4-Dimethylaminophenylazo)benzoic acid

[0179] Molecular Formula: C₁₅H₁₅N₃O₂

[0180] Molecular Weight: 269.31

[0181] CAS: 493-52-7 $\begin{matrix}{{pH} = {4.2\quad {pink}}} \\{= {6.2\quad {yellow}}}\end{matrix}$

[0182] Reichardt's Dye

[0183] Synonyms: [2,6-diphenyl-4-(2,4,6-triphenylpyridinio)phenolate]

[0184] Molecular Formula: C₄₁H₂₉NO

[0185] Molecular Weight: 551.69

[0186] CAS: 10081-39-7

[0187] Nile Red

[0188] Synonyms: 5H-Benzo[a]phenoxazin-5-one, 9-(diethylamino)-(7CI,8CI, 9CI), 9-(Diethylamino)-5H-benzo[a]phenoxazin-5-one; Nile Blue Aoxazone

[0189] Molecular Formula: C₂₀H₁₈N₂O₂

[0190] Molecular Weight: 318.38

[0191] CAS: 7385-67-3

[0192] Congo Red

[0193] Molecular Formula: C₃₂H₂₄N₆O₆S₂.Na₂

[0194] Molecular Weight: 696.67

[0195] CAS: 573-58-0

[0196] pH range: blue 3.1-4.9 red

[0197] Victoria Blue B

[0198] Synonyms: Basic Blue 26, C.I. 44045

[0199] Molecular Formula: C₃₃H₃₂ClN₃

[0200] Molecular Weight: 506.10

[0201] CAS: 2580-56-5

[0202] Eosin Blue

[0203] Synonyms: (Acid Red 91, C.I. 45400,4′,5′-dibromo-2′,7′-dinitrofluorescein, disodium salt)

[0204] Molecular Formula: C₂₀H₈Br₂N₂O₉

[0205] Molecular Weight: 624.08

[0206] CAS: 548-24-3

[0207] Fat Brown B

[0208] Synonyms: Solvent red 3

[0209] Molecular Formula: C₁₈H₁₆N₂O₂

[0210] Molecular Weight: 292.3

[0211] CAS: 6535-42-8

[0212] Benzopurpurin 4B

[0213] Synonyms: (C.I. 23500, Direct Red 2)

[0214] Molecular Formula: C₃₄H₂₈N₆O₆S₂

[0215] Molecular Weight: 724.73

[0216] CAS: 992-59-6

[0217] pH range: violet 1.2-3.8 yellow

[0218] Phloxine B

[0219] Molecular Formula: C₂₀H₄Br₄Cl₄O₅

[0220] CAS: 18472-87-2

[0221] pH range: colorless 2.1-4.1 pink

[0222] Orange G

[0223] Synonyms: 1-Phenylazo-2-naphthol-6,8-disulfonic acid disodiumsalt

[0224] Molecular Formula: C₁₆H₁₀N₂Na₂O₇S₂

[0225] Molecular Weight: 452.

[0226] pH range: yellow 11.5-14.0 pink

[0227] Metanil Yellow

[0228] Synonyms: (Acid Yellow 36, C.I. 13065)

[0229] Molecular Formula: C₁₈H₁₅N₃O₃S.Na

[0230] Molecular Weight: 375.38

[0231] CAS: 587-98-4

[0232] pH 1.5 (red) to pH 2.7 (yellow)

[0233] Naphthol Green B

[0234] Synonyms: (Acid Green 1, C.I. 10020)

[0235] Molecular Formula: C₁₀H₇NO₅S

[0236] Molecular Weight: 878.47

[0237] CAS: 19381-50-1

[0238] Methylene Blue

[0239] Synonyms: (Basic Blue 9, C.I. 52015)

[0240] Molecular Formula: C₁₆H₁₈ClN₃S

[0241] Molecular Weight: 373.90

[0242] CAS: 7220-79-3

[0243] Safranine O

[0244] Synonyms: (C.I. 50240,3,7-diamino-2,8-dimethyl-5-phenylphenazinium chloride)

[0245] Molecular Formula: C₂₀H₁₉ClN₄

[0246] Molecular Weight: 350.85

[0247] CAS: 477-73-6

[0248] Methylene Violet 3RAX

[0249] Synonyms: [3-amino-7-(diethylamino)-5-phenylphenazinium chloride,C.I. 50206, N,N-diethylphenosafranine]

[0250] Molecular Formula: C₂₂H₂₃ClN₄

[0251] Molecular Weight: 378.91

[0252] CAS: 4569-86-2

[0253] Sudan Orange G

[0254] Synonyms: [C.I. 11920, 4-(phenylazo)resorcinol, Solvent Orange 1]

[0255] Molecular Formula: C₆H₅N═NC₆H₃-1,3-(OH)₂

[0256] Molecular Weight: 214.22

[0257] CAS: 2051-85-6

[0258] Morin Hydrate

[0259] Synonyms: (2′,3,4′,5,7-pentahydroxyflavone)

[0260] Molecular Formula: C₁₅H₁₀O₇

[0261] Molecular Weight: 302.24 Neutral Red

[0262] Molecular Formula: C₁₅H₁₆N₄.HCl

[0263] Molecular Weight: 288.78

[0264] CAS: 553-24-2 $\begin{matrix}{{pH} = {6.8\quad {red}}} \\{= {8.0\quad {yellow}}}\end{matrix}$

[0265] Disperse Orange 25

[0266] Molecular Formula: C₁₇H₁₇N₅ 02

[0267] Molecular Weight: 323.36

[0268] CAS: 31482-56-1

[0269] Rosolic Acid

[0270] Molecular Formula: C₂₀H₁₆O₃

[0271] Molecular Weight: 290.32

[0272] CAS: 603-45-2 $\begin{matrix}{{pH} = {5.0\quad {yellow}}} \\{= {6.8\quad {pink}}}\end{matrix}$

[0273] Fat Brown RR

[0274] Molecular Formula: C₁₆H₁₄N₄

[0275] Molecular Weight: 262.32

[0276] CAS: 6416-57-5

[0277] Cyanidin chloride

[0278] Molecular Formula: C15H11O6.Cl

[0279] Molecular Weight: 322.7

[0280] CAS: 528-58-5

[0281] 3,6-Acridineamine

[0282] Molecular Formula: C₁₃H₁₁N₃

[0283] Molecular Weight: 209.25

[0284] CAS Number: 92-62-6

[0285] 6′-Butoxy-2,6-diamino-3,3′-azodipyridine

[0286] Synonym: Azodipyridine

[0287] Molecular Formula: C₁₄H₁₈N₆O

[0288] Molecular Weight: 286.34

[0289] CAS: 617-19-6

[0290] para-Rosaniline Base

[0291] Synonym: Rosaniline

[0292] Molecular Formula: C₁₉H₁₉N₃O

[0293] Molecular Weight: 305.4

[0294] CAS: 25620-78-4

[0295] Acridine Orange Base

[0296] Molecular Formula: C₁₇H₁₉N₃

[0297] Molecular Weight: 265.36

[0298] CAS: 494-38-2

[0299] Crystal Violet

[0300] Molecular Formula: C₂₅H₃₀N₃.Cl

[0301] Molecular Weight: 407.99

[0302] CAS: 548-62-9 $\begin{matrix}{{pH} = {0\quad {yellow}}} \\{= {1.8\quad {blue}}}\end{matrix}$

[0303] Malachite Green Carbinol Base

[0304] Molecular Formula: C₂₃H₂₆N₂O

[0305] Molecular Weight: 346.48

[0306] CAS: 510-13-4 ${pH}\begin{matrix}{{= {0.2\quad {yellow}}}\quad} \\{= {1.8\quad {blue}\text{-}{green}}}\end{matrix}$

[0307] In a preferred embodiment, a low volatility liquid, e.g., aplasticizer, is used in an array of the present invention to keep thedyes in the array from crystallizing and to enhance then response of thearray to an analyte. Examples of suitable low volatility liquidsinclude, but are not limited to DOW CORNING 704 silicone diffusion pumpfluid (Molecular Weight: 484.82, Density: 1.070, CAS Number: 3982-82-9),and diundecyl phthalate (Molecular Weight: 474.73, Density: 0.950, CASNumber: 3648-20-2, Formula: C₃₀H₅₀O₄, Boiling Point (° C.): 523 at 760torr), dibutyl phthalate (Molecular Weight: 278.4, Density: 1.048, CASNumber: 84-74-2, Formula: C₁₆H₂₂O₄, Boiling Point (° C.): 340 at 760torr), diisopropyl phthalate (Molecular Weight: 250.3, Density: 1.063,CAS Number: 605-45-8, Formula: C₁₄H₁₈O₄), squalane (Molecular Weight:422.83, Density: 0.810, CAS Number: 111-01-3, Formula: C₃₀H₆₂, BoilingPoint (° C.): 176 at 0.05 torr), triethylene glycol dimethyl ether(synonym: Trigluyme, Molecular Weight: 178.23, Density: 0.986, CASNumber: 112-49-2, Formula: C₈H₁₈O₄, Boiling Point (° C.): 216 at 760torr), and tetraethlyene glycol dimethyl ether (synonym: Tetraglyme,(Molecular Weight: 222.28, Density: 1.009, CAS Number: 143-24-8,Formula: C₁₀H₂₂O₅, Boiling Point (° C.): 275-276 at 760 torr).

[0308]FIG. 16 illustrates an array containing illustrative examples ofporphyrin, metalloporphyrin, acid-base indicator, and solvatochromaticdyes. Typical sizes can range from 0.5 mm to 2 cm on a side. Linear,hexagonal, or rectangular arrays are also easily used. From left toright and top to bottom the identities and colors of the dyes used inthe illustrative example of FIG. 16 are listed in Table 11 as follows(the exact colors depend, among other things, upon scanner settings).TABLE 11 (Summarizing the Dyes and Colors in FIG. 16, i.e., “Dye -Color”) SnTPPCl₂ - CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - Light CuTPP -Light Green Peach Green Green Brownish Green Salmon AgTPP - NiTPP -InTPPCL - IrTPPCl - ZnTPP - Salmon FeTFPPCl - Salmon Pink Tan Pink OliveZnSi₆PP - ZnSi₇OHPP - ZnSi₈PP - H₂TPP - H₂FPP - Light Alizarin basic -Pink Deep Pink Pink Carmel Brown Violet Me Red - BCP - Dark BCPbasic -BTB - Dark BTB basic - Blue Ph Red basic - Orange Green Blue YellowLavender Nile Red - BCG - Blue BCG basic - CresRed - CresRed basic - CPRed - Violet Blue Brownish Purple Purple Purple R Dye - TB - Yellow TBbasic - MeOr - MeOr basic - CP Red basic - Light Blue Greenish YellowOrangish Brown Bluish Gray Purple

[0309]Zn(Si₈PP)=5,10,15,20-tetrakis(2′,6′-disilyloxyphenyl)porphyrinatozinc(II);

[0310] Me Red=Methyl Red;

[0311] BCP=Bromocresol Purple;

[0312] BTB=Bromothymol Blue;

[0313] Ph Red=Phenol Red;

[0314] BCG=Bromocresol Green;

[0315] CresRed=Cresol Red;

[0316] CP Red=Chlorophenol Red;

[0317] R Dye=Reichardt's Dye;

[0318] TB=Thymol Blue;

[0319] MeOr=Methyl Orange; and

[0320] basic indicates the addition of KOH until the color of the basicform of the indicator dye was observed.

[0321] Note: DOW CORNING 704 silicone diffusion pump fluid (MolecularWeight: 484.82, Density: 1.070, CAS Number: 3982-82-9) was added to allporphyrin solutions: 40 μl/ml.

[0322]FIG. 17 illustrates the response of the array described in FIG. 16to acid vapors, specifically formic acid, acetic acid, iso-valeric acid,and 3-methyl-2-hexenoic acid. As shown in FIG. 17 and summarized inTable 12 below, the color changes of each dye in response to aparticular analyte are shown as color difference maps, as follows (theexact colors depend, among others things, upon scanner settings). Thecolor changes are derived simply by comparing the before exposure andafter exposure colors and subtracting the two images (i.e., the absolutevalue of the difference of the red values becomes the new red value inthe color difference map; etc. for green values and blue values). Ifthere is no change in the red, green, and blue color values of a dye inthe after-exposure image, then the color difference map will show black(i.e., red value=green value=blue value=0). TABLE 12 (Summarizing theDyes and Color Changes in FIG. 17, i.e. “Dye - Difference Map Color”)(Analyte: Formic Acid 140 ppb) SnTPPCl₂ ₋ CoTPP - CrTPPCl MnTPPClFeTPPCl - CuTPP - Black Black (no Black Black Faint Blue Black (no (nochange) (no (no Periphery change) change) change) change) AgTPP -NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black (no Black (no BlackBlack (no Black (no Black (no change) change) (no change) change)change) change) ZnSi₆PP - ZnSi₇OHPP - ZnSi₈PP - H₂TPP - H₂FPP - Alizarinbasic - Black (no Black (no Black (no Black (no Black (no Dark Bluechange) change) change) change) change) Me Red - BCP - BCP basic - BTB -BTB basic - Ph Red basic - Black (no Yellow White Black (no Red Greenchange) change) Periphery w/Yellow Center Nile Red - BCG - BCG CresRed -CresRed CP Red - Black (no Black (no basic - Black (no basic - LightBlack (no change) change) Dark change) Green change) Purple R Dye - TB -Black TB basic - MeOr - MeOr basic - CP Red basic - Black (no (nochange) Black (no Green and Dark Yellow change) change) Purple PurplePeriphery and Purple center (Analyte: Formic Acid 210 ppb) SnTPPCl₂ ₋CoTPP - CrTPPCl - MnTPPCl FeTPPCl - CuTPP - Black Black Black (no Black(no Black (no Black (no (no change) (no change) change) change) change)change) AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - Black FeTFPPCl -Black (no Black (no Black (no Black (no (no change) Black (no change)change) change) change) change) ZnSi₆PP - ZnSi₇OH ZnSi₈PP - H₂TPP -H₂FPP - Black Alizarin basic - Black (no PP - Black (no Black (no (nochange) Black (no change) Black (no change) change) change) change) MeRed - BCP - BCP basic - BTB - BTB basic - Ph Red basic - Black (no RedYellow Black (no Red Green change) Periphery and change) Red Center NileRed - BCG - BCG basic - CresRed - CresRed basic - CP Red - Black Black(no Black (no Red periphery Black (no Green (no change) change) change)change) R Dye - TB - TB basic - MeOr - MeOr basic - CP Red basic - Black(no Black (no Black (no Black (no Black (no Yellow change) change)change) change) change) Periphery and Purple Center (Analyte: FormicAcid 340 ppb) SnTPPCl₂ ₋ CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP -Black Black Black (no Black (no Black (no Black (no (no change) (nochange) change) change) change) change) AgTPP - NiTPP - InTPPCL -IrTPPCl - ZnTPP - FeTFPPCl - Black Black (no Black (no Black (no Black(no Black (no (no change) change) change) change) change) change)ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP - Alizarin basic - Black (noBlack (no Black (no Black (no Black (no Green and Purple change) change)change) change) change) Me Red - BCP - BCP basic - BTB - BTB basic - PhRed basic - Black (no Yellow White Black (no Yellow Green change)change) Nile Red - BCG - Red BCG basic - CresRed - CresRed CP Red -Green Black (no Red and Black (no basic - Light change) Purple change)Green R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Red basic -Black (no (no change) Black (no Blue Purple White change) change)(Analyte: Formic Acid 680 ppb) SnTPPCl₂ ₋ CoTPP - CrTPPCl - MnTPPClFeTPPCl - CuTPP - Black (no Black Black (no Black (no Black (no Black(no change) (no change) change) change) change) change) AgTPP - NiTPP -InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black Black (no Black (no Black(no Black (no Black (no (no change) change) change) change) change)change) ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP - Alizarin basic -Black (no Black (no Black (no Black (no Black (no Green and Purplechange) change) change) change) change) Me Red - BCP - BCP basic - BTB -BTB basic - Ph Red basic - Black (no Yellow White Black (no Red Greenchange) change) Periphery and Yellow Center Nile Red - BCG Red BCGCresRed - CresRed CP Red - Black Black and Purple basic - Red Black (nobasic - Green (no change) (no and Purple change) change) R Dye - TB -Black TB basic - MeOr - MeOr basic - CP Red basic - Black (no (nochange) Black (no Light blue Purple White change) change) (Analyte:Acetic Acid 170 ppb) SnTPPCl₂ ₋ CoTPP - Black CrTPPCl - MnTPPClFeTPPCl - CuTPP - Black (no change) Black (no Black (no Black (no Black(no (no change) change) change) change) change) AgTPP - NiTPP - BlackInTPPCL - IrTPPCl - ZnTPP - Black FeTFPPCl - Black (no (no change) Black(no Black (no (no change) Black (no change) change) change) change)ZnSi₆PP - ZnSi₇OHPP - ZnSi₈PP - H₂TPP - H₂FPP - Black Alizarin basic -Black (no Black (no Black (no Black (no (no change) Black (no change)change) change) change) change) Me Red - BCP - Red BCP basic - BTB - BTBbasic - Ph Red basic - Black (no Orange Black (no Red Black (no change)change) change) Nile Red - BCG - Purple BCG basic - CresRed - CresRedbasic - CP Red. - Black (no and Orange Purple Black (no Black (no Black(no change) Orange change) change) change) R Dye - TB - Black (no TBbasic - MeOr - MeOr basic - CP Red Black (no change) Black (no Black (noBlack (no basic - Black change) change) change) change) (no change)(Analyte: Acetic Acid 250 ppb) SnTPPCl₂ ₋ CoTPP - CrTPPCl - MnTPPCl -FeTPPCl - CuTPP - Black (no Black Black (no Black (no Black (no Black(no change) (no change) change) change) change) change) AgTPP - NiTPP -InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black Black (no Black (no Black(no Black (no Black (no (no change) change) change) change) change)change) ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP - Alizarin basic -Black (no Black (no Black (no Black (no Black (no Black (no change)change) change) change) change) change) Me Red - BCP - BCP basic - BTB -BTB basic - Ph Red basic - Black (no Yellow with Red Black (no Red Greenchange) Red Center change) Nile Red - BCG - BCG basic - CresRed -CresRed CP Red - Black Black (no Orange Red and Black (no basic - (nochange) change) Purple change) Black (no change) R Dye - TB - Black TBbasic - MeOr - MeOr basic - CP Red basic - Black (no (no change) Black(no Black (no Black (no White change) change) change) change) (Analyte:Acetic Acid 340 ppb) SnTPPCl₂ ₋ CoTPP - CrTPPCl - MnTPPCl - FeTPPCl -CuTPP - Black (no Black Black (no Black (no Black (no Black (no change)(no change) change) change) change) change) AgTPP - NiTPP - InTPPCL -IrTPPCl - ZnTPP - FeTFPPCl - Black Black (no Black (no Black (no Black(no Black (no (no change) change) change) change) change) change)ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP - Alizarin basic - Black (noBlack (no Black (no Black (no Black (no Black (no change) change)change) change) change) change) Me Red - BCP - BCP basic - BTB - BTBbasic - Ph Red basic - Black (no Yellow Yellow Black (no Ornage Greenchange) change) Nile Red - BCG - BCG basic - CresRed - CresRed CP Red -Black Black (no Faint Purple Black (no basic - (no change) change)Orange and change) Green Purple R Dye - TB - Black TB basic - MeOr -MeOr basic - CP Red basic - Black (no (no change) Black (no Black (noBlack (no White change) change) change) change) (Analyte: Acetic Acid650 ppb) SnTPPCl ₂ ₋ CoTPP - CrTPPCl - MnTPPCl - n FeTPPCl - CuTPP -Black (no Black Black (no Black (no Black (no Black (no change) (nochange) change) change) change) change) AgTPP - NiTPP - InTPPCL -IrTPPCl - ZnTPP - FeTFPPCl - Black Black (no Black (no Black (no Black(no Black (no (no change) change) change) change) change) change)ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP - Alizarin basic - Black (noBlack (no Black (no Black (no Black (no Faint Green change) change)change) change) change) Me Red - BCP - BCP basic - BTB - BTB basic - PhRed basic - Black (no Yellow and Faint Orange Yellow Green change)Orange) Yellow Nile Red - BCG - BCG basic - CresRed - CresRed CP Red -Faint Black (no Black (no Purple Black (no basic - Green change) change)change) White R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Redbasic - Black (no (no change) Black (no Black (no Green White change)change) change) (Analyte: Iso-Valeric Acid 280 ppb) SnTPPCl₂ ₋ CoTPP -CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black (no Black Black (no Black(no Black (no Black (no change) (no change) change) change) change)change) AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPC - BlackBlack (no Black (no Black (no Black (no Black (no (no change) change)change) change) change) change) ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP -H₂FPP - Alizarin basic - Black (no Black (no Black (no Black (no Black(no Black (no change) change) change) change) change) change) Me Red -BCP - Red BCP basic - BTB - BTB basic - Ph Red basic - Black (no Black(no Faint Red Black (no Orange Orange change) change) change) Nile Red -BCG - BCG basic - CresRed - CresRed CP Red - Black Black (no FaintPurple Red Black (no basic - Dark (no change) change) PeripheryPeriphery change) Green R Dye - TB - Red TB basic - MeOr - MeOr basic -CP Red basic - Black (no and Purple Red Green Green Green Peripherychange) Periphery Periphery Center Periphery (Analyte: Iso-Valeric 420ppb) SnTPPCl₂ ₋ CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - Black (noBlack Black (no Black (no Black (no Black (no change) (no change)change) change) change) change) AgTPP - NiTPP - InTPPCL - IrTPPCl -ZnTPP - FeTFPPCl - Black Black (no Black (no Black (no Black (no Black(no (no change) change) change) change) change) change) ZnSi₆PP -ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP - Alizarin basic - Black (no Black (noBlack (no Black (no Black (no Black (no change) change) change) change)change) change) Me Red - BCP - Red BCP basic - BTB - BTB basic - Ph Redbasic - Black (no Faint Black (no Orange and Faint Orange and change)Green and change) Yellow Green orange Nile Red - BCG - BCG basic -CresRed - CresRed CP Red - Black Black (no Orange Orange Black (nobasic - (no change) change) Periphery change Green R Dye - TB - Black TBbasic - MeOr - MeOr basic - CP Red basic - Black (no (no change) Black(no Green Green Green change) change) (Analyte: Iso-Valeric Acid 850ppb) SnTPPCl₂ ₋ CoTPP - CrTPPCl - MnTPPCl - FeTPPCl - CuTPP - BlackFaint Faint Purple Faint Faint Purple Faint Purple (no change) bluePurple AgTPP - NiTPP - InTPPCL - IrTPPC1 - ZnTPP - FeTFPPCl - BlackFaint Blue Black (no Faint Pink Black (no Black (no (no change) change)change) change) ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP - Alizarinbasic - Faint Blue Faint Blue Black (no Faint Blue Black (no Black (nochange) change) change) Me Red - BCP - White BCP basic - BTB - Blue BTBbasic - Ph Red basic - Black (no and Red Yellow and Red Red and Yellowand Red change) and Red Yellow Nile Red - BCG - White, BCG basic -CresRed - CresRed CP Red - Faint Black (no Red and Blue White Purplebasic - Orange change) and Red Periphery Light Green R Dye - TB - LightTB basic - MeOr - MeOr basic - CP Red basic - Faint Red Blue PurpleGreen and Light Light Green Periphery Periphery Blue Green and RedCenter (Analyte: Iso-Valeric Acid 1700 ppb) SnTPPCl₂ ₋ CoTPP - CrTPPCl -MnTPPCl - FeTPPCl - CuTPP - Black (no Black Black (no Black (no Black(no Black (no change) (no change) change) change) change) change)AgTPP - NiTPP - InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black Black (noBlack (no Black (no Black (no Black (no (no change) change) change)change) change) change) ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP -Alizarin basic - Black (no Black (no Black (no Black (no Black (no FaintPurple change) change) change) change) change) Me Red - BCP - Red BCPbasic - BTB - BTB basic - Ph Red basic - Black (no White Black (no WhiteWhite and Purple change) change) Nile Red - BCG - Red BCG basic -CresRed - CresRed CP Red - Black Black and Purple White, Black (nobasic - (no change) (no Red, and change) White change) Purple R Dye -TB - Black TB basic - MeOr - MeOr basic - CP Red basic - Black (no (nochange) Faint Red Black (no Faint Green change) change) Green (Analyte:3-Methyl-2-hexenoic Acid 12 ppb) SnTPPCl₂ ₋ CoTPP - CrTPPCl - MnTPPCl -FeTPPCl - CuTPP - Black (no Black Black (no Black (no Black (no Black(no change) (no change) change) change) change) change) AgTPP - NiTPP -InTPPCL - IrTPPCl - ZnTPP - FeTFPPCl - Black Black (no Black (no Black(no Black (no Black (no (no change) change) change) change) change)change) ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP - Alizarin basic -Black (no Black (no Black (no Black (no Black (no Black (no change)change) change) change) change) change) Me Red - BCP - Faint BCP basic -BTB - BTB basic - Ph Red basic - Black (no Purple White Black (no RedPurple and Green change) and Purple change) Nile Red - BCG - BCG basic -CresRed - CresRed CP Red - Black Black (no Faint Red Faint Black (nobasic - Light (no change) change) and Purple White and change) Blue andPurple Green R Dye - TB - Black TB basic - MeOr - MeOr basic - CP Redbasic - Black (no (no change) Black (no Black (no Blue and Green change)change) change) Green

[0323]FIG. 18 illustrates a preferred array containing illustrativeexamples of porphyrin, metalloporphyrin, acid-base indicator, andsolvatochromatic dyes. Typical sizes of the array can range from 0.5 mmto 2 cm on a side. Linear, hexagonal or rectangular arrays are alsoeasily used. From left to right and top to bottom the identities andcolors of the dyes used in the illustrative example of FIG. 18 arelisted in Table 13 as follows (the exact colors depend, among otherthings, upon scanner setting). TABLE 13 (Summarizing the Dyes and Colorsin FIG. 18, i.e., “Dye - Color”) SnTPPCl₂- CoTPP - Tan CrTPPCl - GreenMnTPPCl - FeTPPCl - Light CuTPP - Light Green with Dark Green GreenGreen Light Pink Center Zn(C₃F₇)₄P - ZnF₂PP - InTPPCl - ZnTMP - ZnTPP -FeTFPPCl - Gray Light Pink Reddish Beige Pink Salmon Beige ZnSi₆PP -ZnSi₇OHPP - ZnSi₈PP - Light H₂TPP - H₂FPP - Neutral Red Pink Pink PinkLight Greenish Yellow Pink with Reddish Brown Beige Center Methyl Red -Disperse Rosolic Acid - Fat Brown Cyanidin Metanil Orange Orange 25 -Red RR - Dark Chloride - Yellow - Pinkish Reddish Brown Light OrangeYellow Nile Red - Mordant 3,6-Acridineamine Bromocresol Azodipyridine -Rosaniline - Yellow Light Purple Orange 1 - Yellow Green - Pink LightYellow Dark Yellow Reichardt's Acridine Crystal Violet - Thymol BlueCongo Red - Malachite Dye - Teal Orange Dark Blue Purple Dark Red GreenBase - Carbinol Yellow base - Light Blue

[0324] where

[0325] SnTPPCl₂ is 5,10,15,20-Tetraphenyl-21H,23H-porphine Tin(W)Dichloride

[0326] Molecular Formula: C₄₄H₂₈SnCl₂N₄

[0327] Molecular Weight: 802

[0328] CAS: 26334-85-0;

[0329] CoTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine Cobalt(II)

[0330] Molecular Formula: C₄₄H₂₈CoN₄

[0331] Molecular Weight: 671

[0332] CAS: 14172-90-8;

[0333] CrTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine Chromium(III)Chloride

[0334] Molecular Formula: C₄₄H₂₈CrClN₄

[0335] Molecular Weight: 700

[0336] CAS: 28110-70-5;

[0337] MnTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine Manganese(III)Chloride

[0338] Molecular Formula: C₄₄H₂₈ClMnN₄

[0339] Molecular Weight: 703

[0340] CAS: 32195-55-4;

[0341] FeTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine Iron(III)Chloride

[0342] Molecular Formula: C₄₄H₂₈ClFeN₄

[0343] Molecular Weight: 704

[0344] CAS: 16456-81-8;

[0345] CuTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine Copper(II)

[0346] Molecular Formula: C₄₄H₂₈CuN₄

[0347] Molecular Weight: 676

[0348] CAS: 14172-91-9;

[0349] Zn(C₃F₇)₄P is Meso tetra(heptafluoropropyl)porphine Zinc(II)

[0350] Molecular Formula: C₃₂H₈ZnF₂₈N₄

[0351] Molecular Weight: 1044;

[0352] ZnF₂PP is5,10,15,20-Tetrakis(2,6-difluorophenyl)-21H,23H-porphine Zinc(II)

[0353] Molecular Formula: C₄₄H₂₀F₈N₄Zn

[0354] Molecular Weight: 820;

[0355] InTPPCl is 5,10,15,20-Tetraphenyl-21H,23H-porphine Indium(III)Chloride

[0356] Molecular Formula: C₄₄H₂₈ClInN₄

[0357] Molecular Weight: 763;

[0358] ZnTMP is5,10,15,20-Tetrakis(2,4,6-trimethylphenyl)-21H,23H-porphine Zinc(II)

[0359] Molecular Formula: C₅₆H₅₂N₄Zn

[0360] Molecular Weight: 846

[0361] CAS: 104025-54-9;

[0362] ZnTPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine Zinc(II)

[0363] Molecular Formula: C₄₄H₂₈N₄Zn

[0364] Molecular Weight: 678

[0365] CAS: 14074-80-7;

[0366] FeTFPPCl is5,10,15,20-Tetrakis(pentafluorophenyl)-21H,23H-porphine Iron(III)Chloride

[0367] Molecular Formula: C₄₄H₈ClF₂₀FeN₄

[0368] Molecular Weight: 1063.85

[0369] CAS: 36965-71-6;

[0370] ZnSi₆PP is5(phenyl)-10,15,20-trikis(2′,6′-disilyloxyphenyl)porphyrinatozinc(II)

[0371] Molecular Formula: ZnC₈₀H₁₁₂O₆N₄Si₆

[0372] Molecular Weight: 1458;

[0373] ZnSi₇OHPP is5,10,15-trikis(2′,6′-disilyloxyphenyl)-20-(2′-hydroxy-6′-silyloxyphenyl)porphyrinatozinc(II)

[0374] Molecular Formula: ZnC₈₆H₁₂₆O₈N₄Si₇

[0375] Molecular Weight: 1604;

[0376] ZnSi₈PP is5,10,15,20-tetrakis(2′,6′-disilyloxyphenyl)porphyrinatozinc(II)

[0377] Molecular Formula: ZnC₉₂H₁₄₀O₈N₄Si₈

[0378] Molecular Weight: 1718;

[0379] H₂TPP is 5,10,15,20-Tetraphenyl-21H,23H-porphine

[0380] Molecular Formula: C₄₄H₃₀N₄

[0381] Molecular Weight: 614.75

[0382] CAS: 917-23-7;

[0383] H₂FPP is 5,10,15,20-Tetrakis(pentafluorophenyl)-21H,23H-porphine

[0384] Molecular Formula: C₄₄H₁₀F₂₀N₄

[0385] Molecular Weight: 974.57

[0386] CAS: 25440-14-6;

[0387] Azodipyridine is 6′-Butoxy-2,6-diamino-3,3′-azodipyridine

[0388] Molecular Formula: C₁₄H₁₈N₆O

[0389] Molecular Weight: 286.34

[0390] CAS: 617-19-6;

[0391] Rosaniline is Para-Rosaniline Base

[0392] Molecular Formula: C₁₉H₁₉N₃O

[0393] Molecular Weight: 305.4

[0394] CAS: 25620-78-4

[0395]FIG. 19 illustrates the response of the array described in FIG. 18to acetone. As shown in FIG. 18 and summarized in Table 14 below, thecolor changes of each dye in response to aceteone are as follows (theexact colors depend, among other things, upon scanner settings). Thecolor changes are derived simply by comparing the before exposure andafter exposure colors and subtracting the two images (i.e., the absolutevalue of the difference of the red values becomes the new red value inthe color difference map; etc. for green values and blue values). Ifthere is no change in the red, green, and blue color values of a dye inthe after-exposure image, then the color difference map will show black(i.e., red value=green value=blue value=0). TABLE 14 (Summarizing theDyes and Colors in FIG. 19, i.e., “Dye - Color”) SnTPPCl₂ ₋ CoTPP -CrTPPCl - MnTPPCl FeTPPCl - CuTPP - Black Reddish Lavender Gray PinkBlack (no (no change) Brown change) AgTPP - NiTPP - InTPPCL - IrTPPCl -ZnTPP - FeTFPPCl - Dark White Light Teal Blue Light Black (no DarkCobalt Green change) ZnSi₆PP - ZnSi₇OHPP ZnSi₈PP - H₂TPP - H₂FPP -Alizarin basic - Black (no Aqua Dark Teal Green White Dark Purplechange) Periphery and Blue Center Me Red - BCP - BCP basic - BTB - BTBbasic - Ph Red basic - Dark Blue Green Light Light Dark Blue Royal BlueGreen Green Nile Red - BCG - Tan BCG basic - CresRed - CresRed CP Red -Gold Olive Black (no Dark Pink basic - Blue change) R Dye - TB - BrownTB basic - MeOr - MeOr basic - CP Red basic - Light Green Light DarkBlue Black (no change) Pink Green

[0396] Many modifications and variations may be made in the techniquesand structures described and illustrated herein without departing fromthe spirit and scope of the present invention. Accordingly, thetechniques and structures described and illustrated herein should beunderstood to be illustrative only and not limiting upon the scope ofthe present invention.

What is claimed is:
 1. An artificial nose comprising an array, the arraycomprising at least a first dye and a second dye deposited directly ontoa single support in a predetermined pattern combination, the combinationof the dyes in the array having a distinct and direct spectralabsorbance or reflectance response to distinct analytes, wherein thefirst dye and the second are selected from the group of dyes consistingof chemoresponsive dyes, and the second dye is distinct from the firstdye.
 2. The artificial nose of claim 1 wherein the first dye is selectedfrom the group consisting of porphyrin, chlorin, chlorophyll,phtahlocyanine, and salen and their metal complexes.
 3. The artificialnose of claim 1 wherein the second dye is selected from the groupconsisting of acid-base indicator dyes and solvatochromic dyes.
 4. Theartificial nose of claim 1 wherein the first dye is selected from thegroup consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, andsalen and their metal complexes, and the second dye is distinct from thefirst dye and selected from the group of dyes consisting of acid-baseindicator dyes and solvatochromic dyes.
 5. The artificial nose of claim1 wherein the first dye is a metalloporphyrin.
 6. The artificial nose ofclaim 1 wherein the second dye is an acid-base indicator dye.
 7. Theartificial nose of claim 1 wherein the second dye is a solvatochromicdye.
 8. The artificial nose of claim 1 wherein the second dye isselected from the group consisting of Chlorphenol Red, BromocresolGreen, Bromocresol Purple, Bromothymol Blue, Phenol Red, Thymol Blue,Cresol Red, Alizarin, Mordant Orange, Methyl Orange, Methyl Red,Reichardt's Dye, Nile Red, Congo Red, Victoria Blue B, Eosin Blue, FatBrown B, Benzopurpurin 4B, Phloxine B, Orange G, Metanil Yellow,Naphthol Green B, Methylene Blue, Safranine O, Methylene Violet 3RAX,Sudan Orange G, Morin Hydrate, Neutral Red, Disperse Orange 25, RosolicAcid, Fat Brown RR, Cyanidin chloride, 3,6-Acridineamine,6′-Butoxy-2,6-diamino-3,3′-azodipyridine, para-Rosaniline Base, AcridineOrange Base, Crystal Violet, and Malachite Green Carbinol Base.
 9. Theartificial nose of claim 2 wherein the second dye is selected from thegroup consisting of Chlorphenol Red, Bromocresol Green, BromocresolPurple, Bromothymol Blue, Phenol Red, Thymol Blue, Cresol Red, Alizarin,Mordant Orange, Methyl Orange, Methyl Red, Reichardt's Dye, Nile Red,Congo Red, Victoria Blue B, Eosin Blue, Fat Brown B, Benzopurpurin 4B,Phloxine B, Orange G, Metanil Yellow, Naphthol Green B, Methylene Blue,Safranine O, Methylene Violet 3RAX, Sudan Orange G, Morin Hydrate,Neutral Red, Disperse Orange 25, Rosolic Acid, Fat Brown RR, Cyanidinchloride, 3,6-Acridineamine, 6′-Butoxy-2,6-diamino-3,3′-azodipyridine,para-Rosaniline Base, Acridine Orange Base, Crystal Violet, andMalachite Green Carbinol Base.
 10. The artificial nose of claim 1wherein the first dye is a porphyrin and has a periphery and asuperstructure bonded to the periphery.
 11. A method of detecting ananalyte comprising the steps of: forming an array of at least a firstdye and a second dye deposited directly onto a single support in apredetermined pattern combination, the combination of the dyes in thearray having a distinct and direct spectral absorbance or reflectanceresponse to distinct analytes wherein the first dye and the second dyeare selected from the group consisting of chemoresponsive dyes, and thesecond dye is distinct from the first dye, subjecting the array to ananalyte, inspecting the array for a distinct and direct spectralabsorbance or reflectance response, and correlating the distinct anddirect spectral response to the presence of the analyte.
 12. The methodof claim 11 wherein the first dye is selected from the group consistingof porphyrin, chlorin, chlorophyll, phtahlocyanine, and salen and theirmetal complexes.
 13. The method of claim 11 wherein the second dye isselected from the group consisting of acid-base indicator dyes andsolvatochromic dyes.
 14. The method of claim 11 wherein the first dye isselected from the group consisting of porphyrin, chlorin, chlorophyll,phtahlocyanine, and salen and their metal complexes, and the second dyeis distinct from the first dye and selected from the group of acid-baseindicator dyes and solvatochromic dyes.
 15. The method of claim 11wherein the first dye is a metalloporphyrin.
 16. The method of claim 11wherein the second dye is an acid-base indicator dye.
 17. The method ofclaim 11 wherein the second dye is a solvatochromic dye.
 18. The methodof claim 11 wherein the second dye is selected from the group consistingof Chlorphenol Red, Bromocresol Green, Bromocresol Purple, BromothymolBlue, Phenol Red, Thymol Blue, Cresol Red, Alizarin, Mordant Orange,Methyl Orange, Methyl Red, Reichardt's Dye, Nile Red, Congo Red,Victoria Blue B, Eosin Blue, Fat Brown B, Benzopurpurin 4B, Phloxine B,Orange G, Metanil Yellow, Naphthol Green B, Methylene Blue, Safranine O,Methylene Violet 3RAX, Sudan Orange G, Morin Hydrate, Neutral Red,Disperse Orange 25, Rosolic Acid, Fat Brown RR, Cyanidin chloride,3,6-Acridineamine, 6′-Butoxy-2,6-diamino-3,3′-azodipyridine,para-Rosaniline Base, Acridine Orange Base, Crystal Violet, andMalachite Green Carbinol Base.
 19. The method of claim 12 wherein thesecond dye is selected from the group consisting of Chlorphenol Red,Bromocresol Green, Bromocresol Purple, Bromothymol Blue, Phenol Red,Thymol Blue, Cresol Red, Alizarin, Mordant Orange, Methyl Orange, MethylRed, Reichardt's Dye, Nile Red, Congo Red, Victoria Blue B, Eosin Blue,Fat Brown B, Benzopurpurin 4B, Phloxine B, Orange G, Metanil Yellow,Naphthol Green B, Methylene Blue, Safranine O, Methylene Violet 3RAX,Sudan Orange G, Morin Hydrate, Neutral Red, Disperse Orange 25, RosolicAcid, Fat Brown RR, Cyanidin chloride, 3,6-Acridineamine,6′-Butoxy-2,6-diamino-3,3′-azodipyridine, para-Rosaniline Base, AcridineOrange Base, Crystal Violet, and Malachite Green Carbinol Base.
 20. Themethod of claim 11 wherein the first dye is a porphyrin and has aperiphery and a superstructure bonded to the periphery.
 21. Anartificial tongue comprising an array, the array comprising at least afirst dye and a second dye deposited directly onto a single support in apredetermined pattern combination, the combination of the dyes in thearray having a distinct and direct spectral absorbance or reflectanceresponse to distinct analytes in solution or liquid analytes, oranalytes in a solid or solid analytes, wherein the first dye and thesecond dye are selected from the group consisting of chemoresponsivedyes, and the second dye is distinct from the first dye.
 22. Theartificial tongue of claim 21 wherein the first dye is selected from thegroup consisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, andsalen and their metal complexes.
 23. The artificial tongue of claim 21wherein the second dye is selected from the group consisting ofacid-base indicator dyes and solvatochromic dyes.
 24. The artificialtongue of claim 21 wherein the first dye is selected from the groupconsisting of porphyrin, chlorin, chlorophyll, phtahlocyanine, and salenand their metal complexes, and the second dye is distinct from the firstdye and selected from the group of dyes consisting of acid-baseindicator dyes and solvatochromic dyes.
 25. The artificial tongue ofclaim 21 wherein the first dye is a metalloporphyrin.
 26. The artificialtongue of claim 21 wherein the second dye is an acid-base indicator dye.27. The artificial tongue of claim 21 wherein the second dye is asolvatochromic dye.
 28. The artificial tongue of claim 21 wherein thesecond dye is selected from the group consisting of Chlorphenol Red,Bromocresol Green, Bromocresol Purple, Bromothymol Blue, Phenol Red,Thymol Blue, Cresol Red, Alizarin, Mordant Orange, Methyl Orange, MethylRed, Reichardt's Dye, Nile Red, Congo Red, Victoria Blue B, Eosin Blue,Fat Brown B, Benzopurpurin 4B, Phloxine B, Orange G, Metanil Yellow,Naphthol Green B, Methylene Blue, Safranine O, Methylene Violet 3RAX,Sudan Orange G, Morin Hydrate, Neutral Red, Disperse Orange 25, RosolicAcid, Fat Brown RR, Cyanidin chloride, 3,6-Acridineamine,6′-Butoxy-2,6-diamino-3,3′-azodipyridine, para-Rosaniline Base, AcridineOrange Base, Crystal Violet, and Malachite Green Carbinol Base.
 29. Theartificial tongue of claim 22 wherein the second dye is selected fromthe group consisting of Chlorphenol Red, Bromocresol Green, BromocresolPurple, Bromothymol Blue, Phenol Red, Thymol Blue, Cresol Red, Alizarin,Mordant Orange, Methyl Orange, Methyl Red, Reichardt's Dye, Nile Red,Congo Red, Victoria Blue B, Eosin Blue, Fat Brown B, Benzopurpurin 4B,Phloxine B, Orange G, Metanil Yellow, Naphthol Green B, Methylene Blue,Safranine O, Methylene Violet 3RAX, Sudan Orange G, Morin Hydrate,Neutral Red, Disperse Orange 25, Rosolic Acid, Fat Brown RR, Cyanidinchloride, 3,6-Acridineamine, 6′-Butoxy-2,6-diamino-3,3′-azodipyridine,para-Rosaniline Base, Acridine Orange Base, Crystal Violet, andMalachite Green Carbinol Base.
 30. The artificial tongue of claim 21wherein the first dye is a porphyrin and has a periphery and asuperstructure bonded to the periphery.
 31. The artificial nose of claim1 further comprising a low volatility liquid.
 32. The artificial nose ofclaim 2 further comprising a low volatility liquid.
 33. The method ofclaim 11, further comprising the step of adding a low volatility liquidto the array.
 34. The method of claim 12, further comprising the step ofadding a low volatility liquid to the array.
 35. The artificial tongueof claim 21 further comprising a low volatility liquid.
 36. Theartificial tongue of claim 22 further comprising a low volatilityliquid.
 37. The method of claim 11 further comprising the step offorming a table of responses of the array to a plurality of distinctanalytes.
 38. A table of responses of the array of the artificial noseof claim 1 to a plurality of distinct analytes.
 39. A table of responsesof the artificial tongue of claim 21 to a plurality of distinctanalytes.